<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2026 Workiva-->
<!--r:019ff61f-a6da-7f38-8405-aaa151255b49,g:9cae734f-e127-4b95-b8dd-ec9233a294b0-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member"/>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFCHANGESINSTOCKHOLDERSEQUITYUnaudited" xlink:type="simple" xlink:href="vnda-20260930.xsd#CONDENSEDCONSOLIDATEDSTATEMENTSOFCHANGESINSTOCKHOLDERSEQUITYUnaudited"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFCHANGESINSTOCKHOLDERSEQUITYUnaudited" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_019ff61f-a793-70d7-859b-b5c52b7640e6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_019ff61f-a793-7093-b3aa-ecae1aea0cbb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_019ff61f-a793-70d7-859b-b5c52b7640e6" xlink:to="loc_us-gaap_StatementTable_019ff61f-a793-7093-b3aa-ecae1aea0cbb" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_019ff61f-a793-73e5-92cd-995397257fb0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_019ff61f-a793-7093-b3aa-ecae1aea0cbb" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_019ff61f-a793-73e5-92cd-995397257fb0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_019ff61f-a793-73e5-92cd-995397257fb0_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_019ff61f-a793-73e5-92cd-995397257fb0" xlink:to="loc_us-gaap_EquityComponentDomain_019ff61f-a793-73e5-92cd-995397257fb0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_019ff61f-a793-7965-874f-23648fb13926" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_019ff61f-a793-73e5-92cd-995397257fb0" xlink:to="loc_us-gaap_EquityComponentDomain_019ff61f-a793-7965-874f-23648fb13926" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_019ff61f-a793-7103-bf74-76a50720ecc2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019ff61f-a793-7965-874f-23648fb13926" xlink:to="loc_us-gaap_CommonStockMember_019ff61f-a793-7103-bf74-76a50720ecc2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_019ff61f-a793-742c-b4b8-d49a624a359b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019ff61f-a793-7965-874f-23648fb13926" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_019ff61f-a793-742c-b4b8-d49a624a359b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_019ff61f-a793-7a24-8355-aa6eba89b05d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019ff61f-a793-7965-874f-23648fb13926" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_019ff61f-a793-7a24-8355-aa6eba89b05d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_019ff61f-a793-7729-97bd-8618c092813e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019ff61f-a793-7965-874f-23648fb13926" xlink:to="loc_us-gaap_RetainedEarningsMember_019ff61f-a793-7729-97bd-8618c092813e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019ff61f-a793-766c-ae9b-48b0bc33a85f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019ff61f-a793-70d7-859b-b5c52b7640e6" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019ff61f-a793-766c-ae9b-48b0bc33a85f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_019ff61f-a793-7713-ad42-d7f03ff1d914" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019ff61f-a793-766c-ae9b-48b0bc33a85f" xlink:to="loc_us-gaap_CommonStockSharesOutstanding_019ff61f-a793-7713-ad42-d7f03ff1d914" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019ff61f-a793-7fe6-bb73-2227b36547a1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019ff61f-a793-766c-ae9b-48b0bc33a85f" xlink:to="loc_us-gaap_StockholdersEquity_019ff61f-a793-7fe6-bb73-2227b36547a1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_019ff61f-a793-76b7-8178-0787fe939e8a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019ff61f-a793-766c-ae9b-48b0bc33a85f" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_019ff61f-a793-76b7-8178-0787fe939e8a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation_019ff61f-a793-7b8c-8963-76b5b7c595d6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019ff61f-a793-766c-ae9b-48b0bc33a85f" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation_019ff61f-a793-7b8c-8963-76b5b7c595d6" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_019ff61f-a793-7aff-9bee-8ab29eb21158" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019ff61f-a793-766c-ae9b-48b0bc33a85f" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_019ff61f-a793-7aff-9bee-8ab29eb21158" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_019ff61f-a793-7a32-b72a-fd2a2e4a6641" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019ff61f-a793-766c-ae9b-48b0bc33a85f" xlink:to="loc_us-gaap_NetIncomeLoss_019ff61f-a793-7a32-b72a-fd2a2e4a6641" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent_019ff61f-a793-7119-8659-aec725c59aa0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019ff61f-a793-766c-ae9b-48b0bc33a85f" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent_019ff61f-a793-7119-8659-aec725c59aa0" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_019ff61f-a793-7c92-8315-d6c6e3e6851b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019ff61f-a793-7249-9956-9dfc7aa6ea93" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockholdersEquity"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/SummaryofSignificantAccountingPoliciesScheduleofNetProductSalesDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#SummaryofSignificantAccountingPoliciesScheduleofNetProductSalesDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/SummaryofSignificantAccountingPoliciesScheduleofNetProductSalesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EntityWideInformationRevenueFromExternalCustomerLineItems_019ff61f-a794-7fce-9b26-9f7f391cf9d5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EntityWideInformationRevenueFromExternalCustomerLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEntityWideInformationRevenueFromExternalCustomersByProductsAndServicesTable_019ff61f-a794-7836-80c5-4a82f74ece1a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfEntityWideInformationRevenueFromExternalCustomersByProductsAndServicesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EntityWideInformationRevenueFromExternalCustomerLineItems_019ff61f-a794-7fce-9b26-9f7f391cf9d5" xlink:to="loc_us-gaap_ScheduleOfEntityWideInformationRevenueFromExternalCustomersByProductsAndServicesTable_019ff61f-a794-7836-80c5-4a82f74ece1a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019ff61f-a794-72e5-8ff1-4ebd92c733cb" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEntityWideInformationRevenueFromExternalCustomersByProductsAndServicesTable_019ff61f-a794-7836-80c5-4a82f74ece1a" xlink:to="loc_srt_ProductOrServiceAxis_019ff61f-a794-72e5-8ff1-4ebd92c733cb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ff61f-a794-72e5-8ff1-4ebd92c733cb_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019ff61f-a794-72e5-8ff1-4ebd92c733cb" xlink:to="loc_srt_ProductsAndServicesDomain_019ff61f-a794-72e5-8ff1-4ebd92c733cb_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7add-adf9-24209c3bf676" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019ff61f-a794-72e5-8ff1-4ebd92c733cb" xlink:to="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7add-adf9-24209c3bf676" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_FanaptMember_019ff61f-a794-7d4e-8347-3b2f165fe0b7" xlink:href="vnda-20260930.xsd#vnda_FanaptMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7add-adf9-24209c3bf676" xlink:to="loc_vnda_FanaptMember_019ff61f-a794-7d4e-8347-3b2f165fe0b7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_HetliozMember_019ff61f-a794-7374-9e26-7285db6cce6b" xlink:href="vnda-20260930.xsd#vnda_HetliozMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7add-adf9-24209c3bf676" xlink:to="loc_vnda_HetliozMember_019ff61f-a794-7374-9e26-7285db6cce6b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_PONVORYMember_019ff61f-a794-7493-b40e-01096fdc60c9" xlink:href="vnda-20260930.xsd#vnda_PONVORYMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7add-adf9-24209c3bf676" xlink:to="loc_vnda_PONVORYMember_019ff61f-a794-7493-b40e-01096fdc60c9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_NEREUSMember_019ff61f-a794-7e0d-98bc-e4ee58cb0dee" xlink:href="vnda-20260930.xsd#vnda_NEREUSMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7add-adf9-24209c3bf676" xlink:to="loc_vnda_NEREUSMember_019ff61f-a794-7e0d-98bc-e4ee58cb0dee" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019ff61f-a794-7bab-9f79-c50d7e5b24e0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EntityWideInformationRevenueFromExternalCustomerLineItems_019ff61f-a794-7fce-9b26-9f7f391cf9d5" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019ff61f-a794-7bab-9f79-c50d7e5b24e0" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/SummaryofSignificantAccountingPoliciesNarrativeDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#SummaryofSignificantAccountingPoliciesNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/SummaryofSignificantAccountingPoliciesNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_vnda_SummaryOfSignificantAccountingPoliciesLineItems_019ff61f-a794-7533-9fda-de38ca5dde6f" xlink:href="vnda-20260930.xsd#vnda_SummaryOfSignificantAccountingPoliciesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_SummaryOfSignificantAccountingPoliciesTable_019ff61f-a794-7b44-866b-9007a78e99e7" xlink:href="vnda-20260930.xsd#vnda_SummaryOfSignificantAccountingPoliciesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_vnda_SummaryOfSignificantAccountingPoliciesLineItems_019ff61f-a794-7533-9fda-de38ca5dde6f" xlink:to="loc_vnda_SummaryOfSignificantAccountingPoliciesTable_019ff61f-a794-7b44-866b-9007a78e99e7" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019ff61f-a794-7c59-90dc-73982d3b4801" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_SummaryOfSignificantAccountingPoliciesTable_019ff61f-a794-7b44-866b-9007a78e99e7" xlink:to="loc_srt_ProductOrServiceAxis_019ff61f-a794-7c59-90dc-73982d3b4801" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7c59-90dc-73982d3b4801_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019ff61f-a794-7c59-90dc-73982d3b4801" xlink:to="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7c59-90dc-73982d3b4801_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7179-84a3-630e5d017a1b" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019ff61f-a794-7c59-90dc-73982d3b4801" xlink:to="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7179-84a3-630e5d017a1b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_HetliozMember_01a17699-4d5c-716b-a4bc-3475094ab8a5" xlink:href="vnda-20260930.xsd#vnda_HetliozMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7179-84a3-630e5d017a1b" xlink:to="loc_vnda_HetliozMember_01a17699-4d5c-716b-a4bc-3475094ab8a5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_FanaptMember_019ff61f-a794-7a15-93fc-e548a9c67e77" xlink:href="vnda-20260930.xsd#vnda_FanaptMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7179-84a3-630e5d017a1b" xlink:to="loc_vnda_FanaptMember_019ff61f-a794-7a15-93fc-e548a9c67e77" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_PONVORYMember_019ff61f-a794-771f-871a-959011c3eb3b" xlink:href="vnda-20260930.xsd#vnda_PONVORYMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7179-84a3-630e5d017a1b" xlink:to="loc_vnda_PONVORYMember_019ff61f-a794-771f-871a-959011c3eb3b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MajorCustomersAxis_019ff61f-a794-76df-b867-d6b4b76fb64a" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MajorCustomersAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_SummaryOfSignificantAccountingPoliciesTable_019ff61f-a794-7b44-866b-9007a78e99e7" xlink:to="loc_srt_MajorCustomersAxis_019ff61f-a794-76df-b867-d6b4b76fb64a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_019ff61f-a794-76df-b867-d6b4b76fb64a_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_MajorCustomersAxis_019ff61f-a794-76df-b867-d6b4b76fb64a" xlink:to="loc_srt_NameOfMajorCustomerDomain_019ff61f-a794-76df-b867-d6b4b76fb64a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_019ff61f-a794-70ee-ab6f-749b95e87485" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_MajorCustomersAxis_019ff61f-a794-76df-b867-d6b4b76fb64a" xlink:to="loc_srt_NameOfMajorCustomerDomain_019ff61f-a794-70ee-ab6f-749b95e87485" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_FourMajorCustomersMember_01a1634c-ccff-7ca3-ac5a-6bb3f9421b4e" xlink:href="vnda-20260930.xsd#vnda_FourMajorCustomersMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_019ff61f-a794-70ee-ab6f-749b95e87485" xlink:to="loc_vnda_FourMajorCustomersMember_01a1634c-ccff-7ca3-ac5a-6bb3f9421b4e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_019ff61f-a794-7c7b-8908-29f1c4d1fb83" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_SummaryOfSignificantAccountingPoliciesTable_019ff61f-a794-7b44-866b-9007a78e99e7" xlink:to="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_019ff61f-a794-7c7b-8908-29f1c4d1fb83" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019ff61f-a794-7c7b-8908-29f1c4d1fb83_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_019ff61f-a794-7c7b-8908-29f1c4d1fb83" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019ff61f-a794-7c7b-8908-29f1c4d1fb83_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019ff61f-a794-788c-8ee1-afdcd94fb152" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_019ff61f-a794-7c7b-8908-29f1c4d1fb83" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019ff61f-a794-788c-8ee1-afdcd94fb152" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SalesRevenueNetMember_019ff61f-a794-7433-9fb2-638ca40c369a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SalesRevenueNetMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019ff61f-a794-788c-8ee1-afdcd94fb152" xlink:to="loc_us-gaap_SalesRevenueNetMember_019ff61f-a794-7433-9fb2-638ca40c369a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableMember_019ff61f-a794-7469-8b37-aae17e51a82d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccountsReceivableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019ff61f-a794-788c-8ee1-afdcd94fb152" xlink:to="loc_us-gaap_AccountsReceivableMember_019ff61f-a794-7469-8b37-aae17e51a82d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByTypeAxis_019ff61f-a794-78f3-b18a-45ceb34019eb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_SummaryOfSignificantAccountingPoliciesTable_019ff61f-a794-7b44-866b-9007a78e99e7" xlink:to="loc_us-gaap_ConcentrationRiskByTypeAxis_019ff61f-a794-78f3-b18a-45ceb34019eb" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_019ff61f-a794-78f3-b18a-45ceb34019eb_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_019ff61f-a794-78f3-b18a-45ceb34019eb" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_019ff61f-a794-78f3-b18a-45ceb34019eb_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_019ff61f-a794-754f-be23-5313424bbc45" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_019ff61f-a794-78f3-b18a-45ceb34019eb" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_019ff61f-a794-754f-be23-5313424bbc45" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CustomerConcentrationRiskMember_019ff61f-a794-7327-8fb7-b925e8b73d4b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CustomerConcentrationRiskMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_019ff61f-a794-754f-be23-5313424bbc45" xlink:to="loc_us-gaap_CustomerConcentrationRiskMember_019ff61f-a794-7327-8fb7-b925e8b73d4b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditConcentrationRiskMember_019ff61f-a794-7913-a6ea-15b771d725c7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CreditConcentrationRiskMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_019ff61f-a794-754f-be23-5313424bbc45" xlink:to="loc_us-gaap_CreditConcentrationRiskMember_019ff61f-a794-7913-a6ea-15b771d725c7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TimingOfTransferOfGoodOrServiceAxis_01a17a13-08c7-7c4d-8f26-c6e885229f15" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TimingOfTransferOfGoodOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_SummaryOfSignificantAccountingPoliciesTable_019ff61f-a794-7b44-866b-9007a78e99e7" xlink:to="loc_us-gaap_TimingOfTransferOfGoodOrServiceAxis_01a17a13-08c7-7c4d-8f26-c6e885229f15" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TimingOfTransferOfGoodOrServiceDomain_01a17a13-08c7-7c4d-8f26-c6e885229f15_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TimingOfTransferOfGoodOrServiceDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TimingOfTransferOfGoodOrServiceAxis_01a17a13-08c7-7c4d-8f26-c6e885229f15" xlink:to="loc_us-gaap_TimingOfTransferOfGoodOrServiceDomain_01a17a13-08c7-7c4d-8f26-c6e885229f15_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TimingOfTransferOfGoodOrServiceDomain_01a17a13-08c7-738f-a896-c2e1dfe307c4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TimingOfTransferOfGoodOrServiceDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TimingOfTransferOfGoodOrServiceAxis_01a17a13-08c7-7c4d-8f26-c6e885229f15" xlink:to="loc_us-gaap_TimingOfTransferOfGoodOrServiceDomain_01a17a13-08c7-738f-a896-c2e1dfe307c4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransferredAtPointInTimeMember_01a17a13-29b4-7707-b299-a416e8dcb936" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransferredAtPointInTimeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TimingOfTransferOfGoodOrServiceDomain_01a17a13-08c7-738f-a896-c2e1dfe307c4" xlink:to="loc_us-gaap_TransferredAtPointInTimeMember_01a17a13-29b4-7707-b299-a416e8dcb936" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_01a17a11-e303-7531-b209-f65e40b71d13" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_SummaryOfSignificantAccountingPoliciesLineItems_019ff61f-a794-7533-9fda-de38ca5dde6f" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_01a17a11-e303-7531-b209-f65e40b71d13" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCumulativeCatchUpAdjustmentToRevenueChangeInMeasureOfProgress_019ff61f-a794-7b71-a833-f4f1a64c298d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiabilityCumulativeCatchUpAdjustmentToRevenueChangeInMeasureOfProgress"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_SummaryOfSignificantAccountingPoliciesLineItems_019ff61f-a794-7533-9fda-de38ca5dde6f" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCumulativeCatchUpAdjustmentToRevenueChangeInMeasureOfProgress_019ff61f-a794-7b71-a833-f4f1a64c298d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_RevenueFromContractWithCustomerExcludingAssessedTaxEstimateOfPossibleDispute_019ff61f-a794-77c4-ab47-3d33e973cc20" xlink:href="vnda-20260930.xsd#vnda_RevenueFromContractWithCustomerExcludingAssessedTaxEstimateOfPossibleDispute"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_SummaryOfSignificantAccountingPoliciesLineItems_019ff61f-a794-7533-9fda-de38ca5dde6f" xlink:to="loc_vnda_RevenueFromContractWithCustomerExcludingAssessedTaxEstimateOfPossibleDispute_019ff61f-a794-77c4-ab47-3d33e973cc20" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ContractWithCustomerRebateAndChargebackLiability_019ff61f-a794-7735-9ae3-f846f325f287" xlink:href="vnda-20260930.xsd#vnda_ContractWithCustomerRebateAndChargebackLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_SummaryOfSignificantAccountingPoliciesLineItems_019ff61f-a794-7533-9fda-de38ca5dde6f" xlink:to="loc_vnda_ContractWithCustomerRebateAndChargebackLiability_019ff61f-a794-7735-9ae3-f846f325f287" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerRefundLiability_019ff61f-a794-710c-8660-4efa81c266e7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerRefundLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_SummaryOfSignificantAccountingPoliciesLineItems_019ff61f-a794-7533-9fda-de38ca5dde6f" xlink:to="loc_us-gaap_ContractWithCustomerRefundLiability_019ff61f-a794-710c-8660-4efa81c266e7" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskPercentage1_019ff61f-a794-742c-8d96-c949766cd114" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskPercentage1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_SummaryOfSignificantAccountingPoliciesLineItems_019ff61f-a794-7533-9fda-de38ca5dde6f" xlink:to="loc_us-gaap_ConcentrationRiskPercentage1_019ff61f-a794-742c-8d96-c949766cd114" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/MarketableSecuritiesDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#MarketableSecuritiesDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/MarketableSecuritiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019ff61f-a794-7edd-8655-67a3ce27f8a0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_019ff61f-a794-7bbe-b2d1-8157198a462c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtSecuritiesAvailableForSaleTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019ff61f-a794-7edd-8655-67a3ce27f8a0" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_019ff61f-a794-7bbe-b2d1-8157198a462c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_019ff61f-a794-7ff7-ab0e-ab39c0472f3c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_019ff61f-a794-7bbe-b2d1-8157198a462c" xlink:to="loc_us-gaap_FinancialInstrumentAxis_019ff61f-a794-7ff7-ab0e-ab39c0472f3c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019ff61f-a794-7ff7-ab0e-ab39c0472f3c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_019ff61f-a794-7ff7-ab0e-ab39c0472f3c" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019ff61f-a794-7ff7-ab0e-ab39c0472f3c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019ff61f-a794-7c80-aad0-37a6befd610b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_019ff61f-a794-7ff7-ab0e-ab39c0472f3c" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019ff61f-a794-7c80-aad0-37a6befd610b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasuryAndGovernmentMember_019ff61f-a794-7694-8438-69aee6c046dc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_USTreasuryAndGovernmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019ff61f-a794-7c80-aad0-37a6befd610b" xlink:to="loc_us-gaap_USTreasuryAndGovernmentMember_019ff61f-a794-7694-8438-69aee6c046dc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_019ff61f-a794-7a57-b557-6f1d6e77effc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019ff61f-a794-7c80-aad0-37a6befd610b" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_019ff61f-a794-7a57-b557-6f1d6e77effc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostExcludingAccruedInterestAfterAllowanceForCreditLossCurrent_019ff61f-a794-7726-9acd-9b92772756ff" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostExcludingAccruedInterestAfterAllowanceForCreditLossCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019ff61f-a794-7edd-8655-67a3ce27f8a0" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostExcludingAccruedInterestAfterAllowanceForCreditLossCurrent_019ff61f-a794-7726-9acd-9b92772756ff" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_019ff61f-a794-7279-b7e6-e60228d3c578" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019ff61f-a794-7edd-8655-67a3ce27f8a0" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_019ff61f-a794-7279-b7e6-e60228d3c578" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_019ff61f-a794-7491-887f-e2068e7e2261" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019ff61f-a794-7edd-8655-67a3ce27f8a0" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_019ff61f-a794-7491-887f-e2068e7e2261" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterestCurrent_019ff61f-a794-7777-92a7-8878da2a9a30" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterestCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019ff61f-a794-7edd-8655-67a3ce27f8a0" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterestCurrent_019ff61f-a794-7777-92a7-8878da2a9a30" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/FairValueMeasurementsScheduleofAssetsMeasuredatFairValueonRecurringBasisDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#FairValueMeasurementsScheduleofAssetsMeasuredatFairValueonRecurringBasisDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/FairValueMeasurementsScheduleofAssetsMeasuredatFairValueonRecurringBasisDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019ff61f-a794-722f-afb1-57de00d97028" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019ff61f-a794-74ff-9e92-6cd849ed9e9b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019ff61f-a794-722f-afb1-57de00d97028" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019ff61f-a794-74ff-9e92-6cd849ed9e9b" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019ff61f-a794-7c64-8f15-8202bc742884" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019ff61f-a794-74ff-9e92-6cd849ed9e9b" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019ff61f-a794-7c64-8f15-8202bc742884" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019ff61f-a794-7c64-8f15-8202bc742884_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019ff61f-a794-7c64-8f15-8202bc742884" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019ff61f-a794-7c64-8f15-8202bc742884_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019ff61f-a794-7094-91ae-4249f05381a5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019ff61f-a794-7c64-8f15-8202bc742884" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019ff61f-a794-7094-91ae-4249f05381a5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_019ff61f-a794-7ba8-a4b9-0371c3761799" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019ff61f-a794-7094-91ae-4249f05381a5" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_019ff61f-a794-7ba8-a4b9-0371c3761799" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_019ff61f-a794-7b5d-971a-9a9d2b87814f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019ff61f-a794-7094-91ae-4249f05381a5" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_019ff61f-a794-7b5d-971a-9a9d2b87814f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel3Member_019ff61f-a794-7de3-9679-8968c63277b3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueInputsLevel3Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019ff61f-a794-7094-91ae-4249f05381a5" xlink:to="loc_us-gaap_FairValueInputsLevel3Member_019ff61f-a794-7de3-9679-8968c63277b3" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_019ff61f-a794-7d67-8fe5-627bd784fdfe" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019ff61f-a794-74ff-9e92-6cd849ed9e9b" xlink:to="loc_us-gaap_FinancialInstrumentAxis_019ff61f-a794-7d67-8fe5-627bd784fdfe" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019ff61f-a794-7d67-8fe5-627bd784fdfe_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_019ff61f-a794-7d67-8fe5-627bd784fdfe" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019ff61f-a794-7d67-8fe5-627bd784fdfe_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019ff61f-a794-7d90-a04a-d4de74adf1d7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_019ff61f-a794-7d67-8fe5-627bd784fdfe" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019ff61f-a794-7d90-a04a-d4de74adf1d7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasuryAndGovernmentMember_019ff61f-a794-7f79-b964-96e3fd92b4f0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_USTreasuryAndGovernmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019ff61f-a794-7d90-a04a-d4de74adf1d7" xlink:to="loc_us-gaap_USTreasuryAndGovernmentMember_019ff61f-a794-7f79-b964-96e3fd92b4f0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_019ff61f-a794-7719-a866-26e91fee8eee" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019ff61f-a794-7d90-a04a-d4de74adf1d7" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_019ff61f-a794-7719-a866-26e91fee8eee" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterestCurrent_019ff61f-a794-7389-88cb-872217fe9813" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterestCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019ff61f-a794-722f-afb1-57de00d97028" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterestCurrent_019ff61f-a794-7389-88cb-872217fe9813" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_019ff61f-a794-7c74-aea1-f93e69893959" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019ff61f-a794-722f-afb1-57de00d97028" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_019ff61f-a794-7c74-aea1-f93e69893959" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/FairValueMeasurementsNarrativeDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#FairValueMeasurementsNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/FairValueMeasurementsNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019ff61f-a794-792d-8d9e-3b0fbecb45b4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019ff61f-a794-7df5-b352-20eb1749ec9d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019ff61f-a794-792d-8d9e-3b0fbecb45b4" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019ff61f-a794-7df5-b352-20eb1749ec9d" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationAxis_019ff61f-a794-7d68-8791-d5a4df7ec589" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_BalanceSheetLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019ff61f-a794-7df5-b352-20eb1749ec9d" xlink:to="loc_us-gaap_BalanceSheetLocationAxis_019ff61f-a794-7d68-8791-d5a4df7ec589" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_019ff61f-a794-7d68-8791-d5a4df7ec589_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_BalanceSheetLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_019ff61f-a794-7d68-8791-d5a4df7ec589" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_019ff61f-a794-7d68-8791-d5a4df7ec589_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_019ff61f-a794-734c-b2b2-e49fbd88e908" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_BalanceSheetLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_019ff61f-a794-7d68-8791-d5a4df7ec589" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_019ff61f-a794-734c-b2b2-e49fbd88e908" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashEquivalentsMember_019ff61f-a794-7ff1-8daa-57c2fd3f187f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BalanceSheetLocationDomain_019ff61f-a794-734c-b2b2-e49fbd88e908" xlink:to="loc_us-gaap_CashEquivalentsMember_019ff61f-a794-7ff1-8daa-57c2fd3f187f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_019ff61f-a794-701f-90ca-1dc8a59f0332" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019ff61f-a794-792d-8d9e-3b0fbecb45b4" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_019ff61f-a794-701f-90ca-1dc8a59f0332" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/InventoryNarrativeDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#InventoryNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/InventoryNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryLineItems_019ff61f-a794-71bc-ac7e-7a167610af26" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InventoryLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_InventoryTable_019ff61f-a794-7eec-aa3a-e9dac9709771" xlink:href="vnda-20260930.xsd#vnda_InventoryTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_InventoryLineItems_019ff61f-a794-71bc-ac7e-7a167610af26" xlink:to="loc_vnda_InventoryTable_019ff61f-a794-7eec-aa3a-e9dac9709771" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019ff61f-a794-7bf9-bab7-dbacc05ac317" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_InventoryTable_019ff61f-a794-7eec-aa3a-e9dac9709771" xlink:to="loc_srt_ProductOrServiceAxis_019ff61f-a794-7bf9-bab7-dbacc05ac317" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7bf9-bab7-dbacc05ac317_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019ff61f-a794-7bf9-bab7-dbacc05ac317" xlink:to="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7bf9-bab7-dbacc05ac317_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ff61f-a794-72f4-80cc-a7f193793115" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019ff61f-a794-7bf9-bab7-dbacc05ac317" xlink:to="loc_srt_ProductsAndServicesDomain_019ff61f-a794-72f4-80cc-a7f193793115" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_HetliozMember_019ff61f-a794-7a86-850b-07f41d330915" xlink:href="vnda-20260930.xsd#vnda_HetliozMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-72f4-80cc-a7f193793115" xlink:to="loc_vnda_HetliozMember_019ff61f-a794-7a86-850b-07f41d330915" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductAndServiceOtherMember_019ff61f-a794-72d7-93f2-59a10c18c442" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProductAndServiceOtherMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-72f4-80cc-a7f193793115" xlink:to="loc_us-gaap_ProductAndServiceOtherMember_019ff61f-a794-72d7-93f2-59a10c18c442" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_Inventory_019ff61f-a794-7941-b0ba-bea05525e342" xlink:href="vnda-20260930.xsd#vnda_Inventory"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InventoryLineItems_019ff61f-a794-71bc-ac7e-7a167610af26" xlink:to="loc_vnda_Inventory_019ff61f-a794-7941-b0ba-bea05525e342" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/IntangibleAssetsNarrativeDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#IntangibleAssetsNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/IntangibleAssetsNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-7710-962d-a08691eb8c6f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FiniteLivedIntangibleAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019ff61f-a794-7a84-9943-4fadc258c848" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-7710-962d-a08691eb8c6f" xlink:to="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019ff61f-a794-7a84-9943-4fadc258c848" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019ff61f-a794-7508-9e71-6e915802057e" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019ff61f-a794-7a84-9943-4fadc258c848" xlink:to="loc_srt_ProductOrServiceAxis_019ff61f-a794-7508-9e71-6e915802057e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7508-9e71-6e915802057e_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019ff61f-a794-7508-9e71-6e915802057e" xlink:to="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7508-9e71-6e915802057e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7426-a1a0-482b7cb7376e" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019ff61f-a794-7508-9e71-6e915802057e" xlink:to="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7426-a1a0-482b7cb7376e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_HetliozMember_019ff61f-a794-7f2d-a775-672d4e55461e" xlink:href="vnda-20260930.xsd#vnda_HetliozMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7426-a1a0-482b7cb7376e" xlink:to="loc_vnda_HetliozMember_019ff61f-a794-7f2d-a775-672d4e55461e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_NEREUSMember_019ff61f-a794-7064-839c-aac1e97d226f" xlink:href="vnda-20260930.xsd#vnda_NEREUSMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7426-a1a0-482b7cb7376e" xlink:to="loc_vnda_NEREUSMember_019ff61f-a794-7064-839c-aac1e97d226f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_FanaptMember_019ff61f-a794-7b36-ad5d-1363bbe8861b" xlink:href="vnda-20260930.xsd#vnda_FanaptMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7426-a1a0-482b7cb7376e" xlink:to="loc_vnda_FanaptMember_019ff61f-a794-7b36-ad5d-1363bbe8861b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionAxis_019ff61f-a794-71b2-92dc-21bb8e6177c6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019ff61f-a794-7a84-9943-4fadc258c848" xlink:to="loc_us-gaap_AssetAcquisitionAxis_019ff61f-a794-71b2-92dc-21bb8e6177c6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionDomain_019ff61f-a794-71b2-92dc-21bb8e6177c6_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetAcquisitionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AssetAcquisitionAxis_019ff61f-a794-71b2-92dc-21bb8e6177c6" xlink:to="loc_us-gaap_AssetAcquisitionDomain_019ff61f-a794-71b2-92dc-21bb8e6177c6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionDomain_019ff61f-a794-7ed1-961c-725c45210a30" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetAcquisitionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AssetAcquisitionAxis_019ff61f-a794-71b2-92dc-21bb8e6177c6" xlink:to="loc_us-gaap_AssetAcquisitionDomain_019ff61f-a794-7ed1-961c-725c45210a30" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_PONVORYAcquisitionMember_019ff61f-a794-7d41-8790-b1f045b7e258" xlink:href="vnda-20260930.xsd#vnda_PONVORYAcquisitionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionDomain_019ff61f-a794-7ed1-961c-725c45210a30" xlink:to="loc_vnda_PONVORYAcquisitionMember_019ff61f-a794-7d41-8790-b1f045b7e258" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireIntangibleAssets_019ff61f-a794-7083-9dfa-2ff2eb0f9804" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PaymentsToAcquireIntangibleAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-7710-962d-a08691eb8c6f" xlink:to="loc_us-gaap_PaymentsToAcquireIntangibleAssets_019ff61f-a794-7083-9dfa-2ff2eb0f9804" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_CumulativeNetSalesToAchieveMilestone_019ff61f-a794-7e12-9dd8-580b22d66c27" xlink:href="vnda-20260930.xsd#vnda_CumulativeNetSalesToAchieveMilestone"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-7710-962d-a08691eb8c6f" xlink:to="loc_vnda_CumulativeNetSalesToAchieveMilestone_019ff61f-a794-7e12-9dd8-580b22d66c27" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionConsiderationTransferred_019ff61f-a794-7c79-aa65-38f6dcf9e53c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetAcquisitionConsiderationTransferred"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-7710-962d-a08691eb8c6f" xlink:to="loc_us-gaap_AssetAcquisitionConsiderationTransferred_019ff61f-a794-7c79-aa65-38f6dcf9e53c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsGross_019ff61f-a794-7bac-9e8a-2f08a62f336b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FiniteLivedIntangibleAssetsGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-7710-962d-a08691eb8c6f" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsGross_019ff61f-a794-7bac-9e8a-2f08a62f336b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_019ff61f-a794-7225-b30c-648d0b87e1e0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-7710-962d-a08691eb8c6f" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_019ff61f-a794-7225-b30c-648d0b87e1e0" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfIntangibleAssets_019ff61f-a794-76c6-a738-7062e0ef0dc3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AmortizationOfIntangibleAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-7710-962d-a08691eb8c6f" xlink:to="loc_us-gaap_AmortizationOfIntangibleAssets_019ff61f-a794-76c6-a738-7062e0ef0dc3" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/IntangibleAssetsScheduleofIntangibleAssetsDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#IntangibleAssetsScheduleofIntangibleAssetsDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/IntangibleAssetsScheduleofIntangibleAssetsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-76cb-9981-0a8f9495a6f0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FiniteLivedIntangibleAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019ff61f-a794-7b8e-9cc2-1af712fbdff1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-76cb-9981-0a8f9495a6f0" xlink:to="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019ff61f-a794-7b8e-9cc2-1af712fbdff1" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019ff61f-a794-7459-bc8b-6eff86b1e381" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019ff61f-a794-7b8e-9cc2-1af712fbdff1" xlink:to="loc_srt_ProductOrServiceAxis_019ff61f-a794-7459-bc8b-6eff86b1e381" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7459-bc8b-6eff86b1e381_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019ff61f-a794-7459-bc8b-6eff86b1e381" xlink:to="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7459-bc8b-6eff86b1e381_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ff61f-a794-79b4-8378-09fdef2e5f6f" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019ff61f-a794-7459-bc8b-6eff86b1e381" xlink:to="loc_srt_ProductsAndServicesDomain_019ff61f-a794-79b4-8378-09fdef2e5f6f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_HetliozMember_019ff61f-a794-7e85-9b9e-736f53562340" xlink:href="vnda-20260930.xsd#vnda_HetliozMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-79b4-8378-09fdef2e5f6f" xlink:to="loc_vnda_HetliozMember_019ff61f-a794-7e85-9b9e-736f53562340" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_PONVORYMember_019ff61f-a794-72a6-bd82-940ad53d55d9" xlink:href="vnda-20260930.xsd#vnda_PONVORYMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-79b4-8378-09fdef2e5f6f" xlink:to="loc_vnda_PONVORYMember_019ff61f-a794-72a6-bd82-940ad53d55d9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_NEREUSMember_019ff61f-a794-7065-af96-672da2140c95" xlink:href="vnda-20260930.xsd#vnda_NEREUSMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-79b4-8378-09fdef2e5f6f" xlink:to="loc_vnda_NEREUSMember_019ff61f-a794-7065-af96-672da2140c95" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsGross_019ff61f-a794-7d04-a5cb-bdd59cb2905c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FiniteLivedIntangibleAssetsGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-76cb-9981-0a8f9495a6f0" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsGross_019ff61f-a794-7d04-a5cb-bdd59cb2905c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_019ff61f-a794-77bd-8994-6dfc1cb8921a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-76cb-9981-0a8f9495a6f0" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_019ff61f-a794-77bd-8994-6dfc1cb8921a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsNet_019ff61f-a794-7f08-82fe-1f35c231c7cb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FiniteLivedIntangibleAssetsNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-76cb-9981-0a8f9495a6f0" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsNet_019ff61f-a794-7f08-82fe-1f35c231c7cb" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/IntangibleAssetsScheduleofFutureIntangibleAssetAmortizationDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#IntangibleAssetsScheduleofFutureIntangibleAssetAmortizationDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/IntangibleAssetsScheduleofFutureIntangibleAssetAmortizationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-7346-b4fc-107593b40945" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FiniteLivedIntangibleAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019ff61f-a794-7c0b-ad91-183454689b0e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-7346-b4fc-107593b40945" xlink:to="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019ff61f-a794-7c0b-ad91-183454689b0e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019ff61f-a794-7825-b9bb-93254f519001" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019ff61f-a794-7c0b-ad91-183454689b0e" xlink:to="loc_srt_ProductOrServiceAxis_019ff61f-a794-7825-b9bb-93254f519001" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7825-b9bb-93254f519001_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019ff61f-a794-7825-b9bb-93254f519001" xlink:to="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7825-b9bb-93254f519001_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7da7-8f84-dee28ef99dc7" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019ff61f-a794-7825-b9bb-93254f519001" xlink:to="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7da7-8f84-dee28ef99dc7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_HetliozMember_019ff61f-a794-790f-970d-2936984f4c48" xlink:href="vnda-20260930.xsd#vnda_HetliozMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7da7-8f84-dee28ef99dc7" xlink:to="loc_vnda_HetliozMember_019ff61f-a794-790f-970d-2936984f4c48" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_PONVORYMember_019ff61f-a794-798e-9fbe-45cadc40169a" xlink:href="vnda-20260930.xsd#vnda_PONVORYMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7da7-8f84-dee28ef99dc7" xlink:to="loc_vnda_PONVORYMember_019ff61f-a794-798e-9fbe-45cadc40169a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_NEREUSMember_019ff61f-a794-7273-a949-3864a4ba2fe0" xlink:href="vnda-20260930.xsd#vnda_NEREUSMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7da7-8f84-dee28ef99dc7" xlink:to="loc_vnda_NEREUSMember_019ff61f-a794-7273-a949-3864a4ba2fe0" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsNet_019ff61f-a794-7791-a72e-4b9553ffb897" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FiniteLivedIntangibleAssetsNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-7346-b4fc-107593b40945" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsNet_019ff61f-a794-7791-a72e-4b9553ffb897" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseRemainderOfFiscalYear_019ff61f-a794-7354-9c61-3ae904eae12f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseRemainderOfFiscalYear"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-7346-b4fc-107593b40945" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseRemainderOfFiscalYear_019ff61f-a794-7354-9c61-3ae904eae12f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths_019ff61f-a794-7ef0-b277-51eaa812acee" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-7346-b4fc-107593b40945" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths_019ff61f-a794-7ef0-b277-51eaa812acee" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo_019ff61f-a794-7578-a72c-4f7475e880f3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-7346-b4fc-107593b40945" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo_019ff61f-a794-7578-a72c-4f7475e880f3" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree_019ff61f-a794-724b-ae3c-d6dec592e167" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-7346-b4fc-107593b40945" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree_019ff61f-a794-724b-ae3c-d6dec592e167" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour_019ff61f-a794-7ae2-be64-245680eaf3ad" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-7346-b4fc-107593b40945" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour_019ff61f-a794-7ae2-be64-245680eaf3ad" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_FiniteLivedIntangibleAssetExpectedAmortizationAfterYearFour_019ff61f-a794-765d-8587-e6c49d32e286" xlink:href="vnda-20260930.xsd#vnda_FiniteLivedIntangibleAssetExpectedAmortizationAfterYearFour"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019ff61f-a794-7346-b4fc-107593b40945" xlink:to="loc_vnda_FiniteLivedIntangibleAssetExpectedAmortizationAfterYearFour_019ff61f-a794-765d-8587-e6c49d32e286" xlink:type="arc" order="6"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/CommitmentsandContingenciesFanaptNarrativeDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#CommitmentsandContingenciesFanaptNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/CommitmentsandContingenciesFanaptNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a794-78e0-8785-71fc4ca0b036" xlink:href="vnda-20260930.xsd#vnda_CommitmentsAndContingenciesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a794-7606-bed2-503cdb6d4db6" xlink:href="vnda-20260930.xsd#vnda_CommitmentsAndContingenciesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a794-78e0-8785-71fc4ca0b036" xlink:to="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a794-7606-bed2-503cdb6d4db6" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019ff61f-a794-7bd0-9cf5-0a743e962d65" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a794-7606-bed2-503cdb6d4db6" xlink:to="loc_srt_ProductOrServiceAxis_019ff61f-a794-7bd0-9cf5-0a743e962d65" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7bd0-9cf5-0a743e962d65_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019ff61f-a794-7bd0-9cf5-0a743e962d65" xlink:to="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7bd0-9cf5-0a743e962d65_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7268-9399-df2fc5e4c527" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019ff61f-a794-7bd0-9cf5-0a743e962d65" xlink:to="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7268-9399-df2fc5e4c527" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_FanaptMember_019ff61f-a794-7c76-8196-605bd4a7da29" xlink:href="vnda-20260930.xsd#vnda_FanaptMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7268-9399-df2fc5e4c527" xlink:to="loc_vnda_FanaptMember_019ff61f-a794-7c76-8196-605bd4a7da29" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_RoyaltyPayableOnNetSalesPercentage_019ff61f-a794-76c8-9bc4-56720e6ba437" xlink:href="vnda-20260930.xsd#vnda_RoyaltyPayableOnNetSalesPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a794-78e0-8785-71fc4ca0b036" xlink:to="loc_vnda_RoyaltyPayableOnNetSalesPercentage_019ff61f-a794-76c8-9bc4-56720e6ba437" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_RoyaltyPeriod_019ff61f-a794-7008-a024-bc1376c5723d" xlink:href="vnda-20260930.xsd#vnda_RoyaltyPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a794-78e0-8785-71fc4ca0b036" xlink:to="loc_vnda_RoyaltyPeriod_019ff61f-a794-7008-a024-bc1376c5723d" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/CommitmentsandContingenciesHETLIOZNarrativeDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#CommitmentsandContingenciesHETLIOZNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/CommitmentsandContingenciesHETLIOZNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a794-7000-9d8f-f036859b8467" xlink:href="vnda-20260930.xsd#vnda_CommitmentsAndContingenciesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a794-7d37-8e44-8e0256ee68c3" xlink:href="vnda-20260930.xsd#vnda_CommitmentsAndContingenciesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a794-7000-9d8f-f036859b8467" xlink:to="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a794-7d37-8e44-8e0256ee68c3" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019ff61f-a794-7c63-bee0-4148fa04ce14" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a794-7d37-8e44-8e0256ee68c3" xlink:to="loc_srt_ProductOrServiceAxis_019ff61f-a794-7c63-bee0-4148fa04ce14" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7c63-bee0-4148fa04ce14_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019ff61f-a794-7c63-bee0-4148fa04ce14" xlink:to="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7c63-bee0-4148fa04ce14_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7f5e-8315-ae8cdd1f939a" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019ff61f-a794-7c63-bee0-4148fa04ce14" xlink:to="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7f5e-8315-ae8cdd1f939a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_HetliozMember_019ff61f-a794-70ec-bbe7-acd6d3b5ea7f" xlink:href="vnda-20260930.xsd#vnda_HetliozMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7f5e-8315-ae8cdd1f939a" xlink:to="loc_vnda_HetliozMember_019ff61f-a794-70ec-bbe7-acd6d3b5ea7f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementGeographicalAxis_019ff61f-a794-7518-9b68-4a22e8becdaa" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_StatementGeographicalAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a794-7d37-8e44-8e0256ee68c3" xlink:to="loc_srt_StatementGeographicalAxis_019ff61f-a794-7518-9b68-4a22e8becdaa" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_019ff61f-a794-7518-9b68-4a22e8becdaa_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementGeographicalAxis_019ff61f-a794-7518-9b68-4a22e8becdaa" xlink:to="loc_srt_SegmentGeographicalDomain_019ff61f-a794-7518-9b68-4a22e8becdaa_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_019ff61f-a794-74b2-aeb8-ab8211f57a6d" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementGeographicalAxis_019ff61f-a794-7518-9b68-4a22e8becdaa" xlink:to="loc_srt_SegmentGeographicalDomain_019ff61f-a794-74b2-aeb8-ab8211f57a6d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NonUsMember_019ff61f-a794-733f-9612-c0baf776fa9b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NonUsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_019ff61f-a794-74b2-aeb8-ab8211f57a6d" xlink:to="loc_us-gaap_NonUsMember_019ff61f-a794-733f-9612-c0baf776fa9b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireIntangibleAssets_019ff61f-a794-7b82-9355-942fba8a82df" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PaymentsToAcquireIntangibleAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a794-7000-9d8f-f036859b8467" xlink:to="loc_us-gaap_PaymentsToAcquireIntangibleAssets_019ff61f-a794-7b82-9355-942fba8a82df" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsPeriodIncreaseDecrease_019ff61f-a794-718b-b5a5-85766bc3d306" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FiniteLivedIntangibleAssetsPeriodIncreaseDecrease"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a794-7000-9d8f-f036859b8467" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsPeriodIncreaseDecrease_019ff61f-a794-718b-b5a5-85766bc3d306" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_DevelopmentAndMilestonePaymentsPotentiallyDueToThirdParty_019ff61f-a794-7489-b481-d3dfcbb75744" xlink:href="vnda-20260930.xsd#vnda_DevelopmentAndMilestonePaymentsPotentiallyDueToThirdParty"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a794-7000-9d8f-f036859b8467" xlink:to="loc_vnda_DevelopmentAndMilestonePaymentsPotentiallyDueToThirdParty_019ff61f-a794-7489-b481-d3dfcbb75744" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_RoyaltyPeriod_019ff61f-a794-7a81-9dcb-5c1cd92c502d" xlink:href="vnda-20260930.xsd#vnda_RoyaltyPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a794-7000-9d8f-f036859b8467" xlink:to="loc_vnda_RoyaltyPeriod_019ff61f-a794-7a81-9dcb-5c1cd92c502d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_RoyaltyPayableOnNetSalesPercentage_019ff61f-a794-794f-9aea-a717124882df" xlink:href="vnda-20260930.xsd#vnda_RoyaltyPayableOnNetSalesPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a794-7000-9d8f-f036859b8467" xlink:to="loc_vnda_RoyaltyPayableOnNetSalesPercentage_019ff61f-a794-794f-9aea-a717124882df" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_PercentageOfFutureSublicenseFeesPayable_019ff61f-a794-7702-9583-5ee63092efc3" xlink:href="vnda-20260930.xsd#vnda_PercentageOfFutureSublicenseFeesPayable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a794-7000-9d8f-f036859b8467" xlink:to="loc_vnda_PercentageOfFutureSublicenseFeesPayable_019ff61f-a794-7702-9583-5ee63092efc3" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/CommitmentsandContingenciesNEREUSNarrativeDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#CommitmentsandContingenciesNEREUSNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/CommitmentsandContingenciesNEREUSNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a794-74ab-ae28-5888b5a4de18" xlink:href="vnda-20260930.xsd#vnda_CommitmentsAndContingenciesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a794-7c79-a838-f5a134fc5731" xlink:href="vnda-20260930.xsd#vnda_CommitmentsAndContingenciesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a794-74ab-ae28-5888b5a4de18" xlink:to="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a794-7c79-a838-f5a134fc5731" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_019ff61f-a794-7750-a96e-5798b6ed7cda" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a794-7c79-a838-f5a134fc5731" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_019ff61f-a794-7750-a96e-5798b6ed7cda" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_019ff61f-a794-7750-a96e-5798b6ed7cda_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_019ff61f-a794-7750-a96e-5798b6ed7cda" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_019ff61f-a794-7750-a96e-5798b6ed7cda_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_019ff61f-a794-7290-b591-630171ed6eb9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_019ff61f-a794-7750-a96e-5798b6ed7cda" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_019ff61f-a794-7290-b591-630171ed6eb9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_NDAApprovalMilestonesMember_019ff61f-a794-7a92-9c62-d7ac4faca9c8" xlink:href="vnda-20260930.xsd#vnda_NDAApprovalMilestonesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_019ff61f-a794-7290-b591-630171ed6eb9" xlink:to="loc_vnda_NDAApprovalMilestonesMember_019ff61f-a794-7a92-9c62-d7ac4faca9c8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_RegulatoryApprovalMilestoneMember_019ff61f-a794-7f51-98e9-0a0247793c39" xlink:href="vnda-20260930.xsd#vnda_RegulatoryApprovalMilestoneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_019ff61f-a794-7290-b591-630171ed6eb9" xlink:to="loc_vnda_RegulatoryApprovalMilestoneMember_019ff61f-a794-7f51-98e9-0a0247793c39" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_SalesMilestoneMember_019ff61f-a794-7086-bb13-6bd2ebb46bdf" xlink:href="vnda-20260930.xsd#vnda_SalesMilestoneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_019ff61f-a794-7290-b591-630171ed6eb9" xlink:to="loc_vnda_SalesMilestoneMember_019ff61f-a794-7086-bb13-6bd2ebb46bdf" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementGeographicalAxis_019ff61f-a794-74d2-a72a-59728571917e" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_StatementGeographicalAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a794-7c79-a838-f5a134fc5731" xlink:to="loc_srt_StatementGeographicalAxis_019ff61f-a794-74d2-a72a-59728571917e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_019ff61f-a794-74d2-a72a-59728571917e_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementGeographicalAxis_019ff61f-a794-74d2-a72a-59728571917e" xlink:to="loc_srt_SegmentGeographicalDomain_019ff61f-a794-74d2-a72a-59728571917e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_019ff61f-a794-73f3-9034-c5f43fe41471" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementGeographicalAxis_019ff61f-a794-74d2-a72a-59728571917e" xlink:to="loc_srt_SegmentGeographicalDomain_019ff61f-a794-73f3-9034-c5f43fe41471" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EuropeanUnionMember_019ff61f-a794-7cb8-955e-030371941a33" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EuropeanUnionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_019ff61f-a794-73f3-9034-c5f43fe41471" xlink:to="loc_us-gaap_EuropeanUnionMember_019ff61f-a794-7cb8-955e-030371941a33" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019ff61f-a794-77bd-870f-ee72355dfde5" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a794-7c79-a838-f5a134fc5731" xlink:to="loc_srt_ProductOrServiceAxis_019ff61f-a794-77bd-870f-ee72355dfde5" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ff61f-a794-77bd-870f-ee72355dfde5_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019ff61f-a794-77bd-870f-ee72355dfde5" xlink:to="loc_srt_ProductsAndServicesDomain_019ff61f-a794-77bd-870f-ee72355dfde5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7d65-9f09-b02fb57805d6" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019ff61f-a794-77bd-870f-ee72355dfde5" xlink:to="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7d65-9f09-b02fb57805d6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_NEREUSMember_019ff61f-a794-7ab4-a703-98e7acc725dd" xlink:href="vnda-20260930.xsd#vnda_NEREUSMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a794-7d65-9f09-b02fb57805d6" xlink:to="loc_vnda_NEREUSMember_019ff61f-a794-7ab4-a703-98e7acc725dd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_FuturePercentageOfRoyaltyPaymentsBasedOnNetSales_019ff61f-a794-7c1b-8e69-410a4ec6494d" xlink:href="vnda-20260930.xsd#vnda_FuturePercentageOfRoyaltyPaymentsBasedOnNetSales"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a794-74ab-ae28-5888b5a4de18" xlink:to="loc_vnda_FuturePercentageOfRoyaltyPaymentsBasedOnNetSales_019ff61f-a794-7c1b-8e69-410a4ec6494d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_DevelopmentAndMilestoneObligationsPaidToThirdParty_019ff61f-a794-7dd0-b92f-93a2ee53a06c" xlink:href="vnda-20260930.xsd#vnda_DevelopmentAndMilestoneObligationsPaidToThirdParty"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a794-74ab-ae28-5888b5a4de18" xlink:to="loc_vnda_DevelopmentAndMilestoneObligationsPaidToThirdParty_019ff61f-a794-7dd0-b92f-93a2ee53a06c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_DevelopmentAndMilestonePaymentsPotentiallyDueToThirdParty_019ff61f-a794-7b84-b586-3a44120f66d1" xlink:href="vnda-20260930.xsd#vnda_DevelopmentAndMilestonePaymentsPotentiallyDueToThirdParty"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a794-74ab-ae28-5888b5a4de18" xlink:to="loc_vnda_DevelopmentAndMilestonePaymentsPotentiallyDueToThirdParty_019ff61f-a794-7b84-b586-3a44120f66d1" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/CommitmentsandContingenciesQuimilzaNarrativeDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#CommitmentsandContingenciesQuimilzaNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/CommitmentsandContingenciesQuimilzaNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-77fe-ad3a-64a0d3f73316" xlink:href="vnda-20260930.xsd#vnda_CommitmentsAndContingenciesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a794-74a0-b75a-f36b3cb6adce" xlink:href="vnda-20260930.xsd#vnda_CommitmentsAndContingenciesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-77fe-ad3a-64a0d3f73316" xlink:to="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a794-74a0-b75a-f36b3cb6adce" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_019ff61f-a794-7967-bc78-fc51f4d9196d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a794-74a0-b75a-f36b3cb6adce" xlink:to="loc_us-gaap_TypeOfArrangementAxis_019ff61f-a794-7967-bc78-fc51f4d9196d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019ff61f-a794-7967-bc78-fc51f4d9196d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_019ff61f-a794-7967-bc78-fc51f4d9196d" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019ff61f-a794-7967-bc78-fc51f4d9196d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019ff61f-a794-796f-8d0f-8cbcd3dcaf20" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_019ff61f-a794-7967-bc78-fc51f4d9196d" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019ff61f-a794-796f-8d0f-8cbcd3dcaf20" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_QuimilzaMember_019ff61f-a794-7f34-a901-fae744da7931" xlink:href="vnda-20260930.xsd#vnda_QuimilzaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019ff61f-a794-796f-8d0f-8cbcd3dcaf20" xlink:to="loc_vnda_QuimilzaMember_019ff61f-a794-7f34-a901-fae744da7931" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_019ff61f-a794-7e63-a62b-4e861e771407" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a794-74a0-b75a-f36b3cb6adce" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_019ff61f-a794-7e63-a62b-4e861e771407" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_019ff61f-a794-7e63-a62b-4e861e771407_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_019ff61f-a794-7e63-a62b-4e861e771407" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_019ff61f-a794-7e63-a62b-4e861e771407_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_019ff61f-a794-73e6-bf6e-bc152e48923e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_019ff61f-a794-7e63-a62b-4e861e771407" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_019ff61f-a794-73e6-bf6e-bc152e48923e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_FutureRegulatoryApprovalAndSalesMilestonesMember_019ff61f-a794-7abe-bc5d-1a56257e8d5a" xlink:href="vnda-20260930.xsd#vnda_FutureRegulatoryApprovalAndSalesMilestonesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_019ff61f-a794-73e6-bf6e-bc152e48923e" xlink:to="loc_vnda_FutureRegulatoryApprovalAndSalesMilestonesMember_019ff61f-a794-7abe-bc5d-1a56257e8d5a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_FutureRegulatoryApprovalFilingApplicationForMarketingAuthorizationMilestoneMember_019ff61f-a794-7596-b5c3-2d9645d03766" xlink:href="vnda-20260930.xsd#vnda_FutureRegulatoryApprovalFilingApplicationForMarketingAuthorizationMilestoneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_FutureRegulatoryApprovalAndSalesMilestonesMember_019ff61f-a794-7abe-bc5d-1a56257e8d5a" xlink:to="loc_vnda_FutureRegulatoryApprovalFilingApplicationForMarketingAuthorizationMilestoneMember_019ff61f-a794-7596-b5c3-2d9645d03766" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_FutureRegulatoryApprovalSalesMilestonesMember_019ff61f-a794-7041-97de-edd476493583" xlink:href="vnda-20260930.xsd#vnda_FutureRegulatoryApprovalSalesMilestonesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_FutureRegulatoryApprovalAndSalesMilestonesMember_019ff61f-a794-7abe-bc5d-1a56257e8d5a" xlink:to="loc_vnda_FutureRegulatoryApprovalSalesMilestonesMember_019ff61f-a794-7041-97de-edd476493583" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementGeographicalAxis_019ff61f-a794-7ba6-8bb4-5cdf63001a25" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_StatementGeographicalAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a794-74a0-b75a-f36b3cb6adce" xlink:to="loc_srt_StatementGeographicalAxis_019ff61f-a794-7ba6-8bb4-5cdf63001a25" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_019ff61f-a794-7ba6-8bb4-5cdf63001a25_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementGeographicalAxis_019ff61f-a794-7ba6-8bb4-5cdf63001a25" xlink:to="loc_srt_SegmentGeographicalDomain_019ff61f-a794-7ba6-8bb4-5cdf63001a25_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_019ff61f-a794-7c14-9c8b-435230144bdd" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementGeographicalAxis_019ff61f-a794-7ba6-8bb4-5cdf63001a25" xlink:to="loc_srt_SegmentGeographicalDomain_019ff61f-a794-7c14-9c8b-435230144bdd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_country_US_019ff61f-a835-776f-ad06-d7f4afda5bbc" xlink:href="https://xbrl.sec.gov/country/2025/country-2025.xsd#country_US"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_019ff61f-a794-7c14-9c8b-435230144bdd" xlink:to="loc_country_US_019ff61f-a835-776f-ad06-d7f4afda5bbc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EuropeMember_019ff61f-a835-750b-abc4-c632fed0b3ab" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_EuropeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_019ff61f-a794-7c14-9c8b-435230144bdd" xlink:to="loc_srt_EuropeMember_019ff61f-a835-750b-abc4-c632fed0b3ab" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_DevelopmentAndMilestoneObligationsPaidToThirdParty_019ff61f-a835-7eae-bbc9-fbd2ad629dcd" xlink:href="vnda-20260930.xsd#vnda_DevelopmentAndMilestoneObligationsPaidToThirdParty"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-77fe-ad3a-64a0d3f73316" xlink:to="loc_vnda_DevelopmentAndMilestoneObligationsPaidToThirdParty_019ff61f-a835-7eae-bbc9-fbd2ad629dcd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_AdditionalDevelopmentAndMilestoneObligationsPaidToThirdParty_019ff61f-a835-75c5-8798-bd983fd8f4cb" xlink:href="vnda-20260930.xsd#vnda_AdditionalDevelopmentAndMilestoneObligationsPaidToThirdParty"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-77fe-ad3a-64a0d3f73316" xlink:to="loc_vnda_AdditionalDevelopmentAndMilestoneObligationsPaidToThirdParty_019ff61f-a835-75c5-8798-bd983fd8f4cb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_019ff61f-a835-7ac4-a5f9-4a2525937144" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-77fe-ad3a-64a0d3f73316" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_019ff61f-a835-7ac4-a5f9-4a2525937144" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_RoyaltyPayableOnNetSalesPercentage_019ff61f-a835-7155-aa98-cc43daa735e1" xlink:href="vnda-20260930.xsd#vnda_RoyaltyPayableOnNetSalesPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-77fe-ad3a-64a0d3f73316" xlink:to="loc_vnda_RoyaltyPayableOnNetSalesPercentage_019ff61f-a835-7155-aa98-cc43daa735e1" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_DevelopmentAndMilestonePaymentsPotentiallyDueToThirdParty_019ff61f-a835-7190-ac46-565033a3b91e" xlink:href="vnda-20260930.xsd#vnda_DevelopmentAndMilestonePaymentsPotentiallyDueToThirdParty"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-77fe-ad3a-64a0d3f73316" xlink:to="loc_vnda_DevelopmentAndMilestonePaymentsPotentiallyDueToThirdParty_019ff61f-a835-7190-ac46-565033a3b91e" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/CommitmentsandContingenciesPortfolioofCFTRActivatorsandInhibitorsNarrativeDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#CommitmentsandContingenciesPortfolioofCFTRActivatorsandInhibitorsNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/CommitmentsandContingenciesPortfolioofCFTRActivatorsandInhibitorsNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-7a46-9cca-ab7b817e6a5a" xlink:href="vnda-20260930.xsd#vnda_CommitmentsAndContingenciesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a835-7aa3-846c-34a6820ac97a" xlink:href="vnda-20260930.xsd#vnda_CommitmentsAndContingenciesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-7a46-9cca-ab7b817e6a5a" xlink:to="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a835-7aa3-846c-34a6820ac97a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019ff61f-a835-7f62-ae22-0c9797611bb7" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a835-7aa3-846c-34a6820ac97a" xlink:to="loc_srt_ProductOrServiceAxis_019ff61f-a835-7f62-ae22-0c9797611bb7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ff61f-a835-7f62-ae22-0c9797611bb7_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019ff61f-a835-7f62-ae22-0c9797611bb7" xlink:to="loc_srt_ProductsAndServicesDomain_019ff61f-a835-7f62-ae22-0c9797611bb7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ff61f-a835-77e6-ae0b-09a5815856ce" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019ff61f-a835-7f62-ae22-0c9797611bb7" xlink:to="loc_srt_ProductsAndServicesDomain_019ff61f-a835-77e6-ae0b-09a5815856ce" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_CftrActivatorsAndInhibitorsMember_019ff61f-a835-70c6-9638-2552206aefb5" xlink:href="vnda-20260930.xsd#vnda_CftrActivatorsAndInhibitorsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ff61f-a835-77e6-ae0b-09a5815856ce" xlink:to="loc_vnda_CftrActivatorsAndInhibitorsMember_019ff61f-a835-70c6-9638-2552206aefb5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_019ff61f-a835-7b01-bcb7-bf590f940d0a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a835-7aa3-846c-34a6820ac97a" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_019ff61f-a835-7b01-bcb7-bf590f940d0a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_019ff61f-a835-7b01-bcb7-bf590f940d0a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_019ff61f-a835-7b01-bcb7-bf590f940d0a" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_019ff61f-a835-7b01-bcb7-bf590f940d0a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_019ff61f-a835-7d6d-a7e4-0b9bf44d0c83" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_019ff61f-a835-7b01-bcb7-bf590f940d0a" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_019ff61f-a835-7d6d-a7e4-0b9bf44d0c83" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_DevelopmentMilestonesMember_019ff61f-a835-7eb1-a757-3b4651e2f41a" xlink:href="vnda-20260930.xsd#vnda_DevelopmentMilestonesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_019ff61f-a835-7d6d-a7e4-0b9bf44d0c83" xlink:to="loc_vnda_DevelopmentMilestonesMember_019ff61f-a835-7eb1-a757-3b4651e2f41a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_FutureRegulatoryApprovalAndSalesMilestonesMember_019ff61f-a835-74fc-afa4-b0bfa310ca38" xlink:href="vnda-20260930.xsd#vnda_FutureRegulatoryApprovalAndSalesMilestonesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_019ff61f-a835-7d6d-a7e4-0b9bf44d0c83" xlink:to="loc_vnda_FutureRegulatoryApprovalAndSalesMilestonesMember_019ff61f-a835-74fc-afa4-b0bfa310ca38" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_DevelopmentAndMilestonePaymentConclusionOfClinicalStudiesMember_019ff61f-a835-7ca5-84e7-6cf43f396036" xlink:href="vnda-20260930.xsd#vnda_DevelopmentAndMilestonePaymentConclusionOfClinicalStudiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_019ff61f-a835-7d6d-a7e4-0b9bf44d0c83" xlink:to="loc_vnda_DevelopmentAndMilestonePaymentConclusionOfClinicalStudiesMember_019ff61f-a835-7ca5-84e7-6cf43f396036" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_019ff61f-a835-7bcf-b443-740a9ab0ed07" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a835-7aa3-846c-34a6820ac97a" xlink:to="loc_srt_RangeAxis_019ff61f-a835-7bcf-b443-740a9ab0ed07" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019ff61f-a835-7bcf-b443-740a9ab0ed07_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_019ff61f-a835-7bcf-b443-740a9ab0ed07" xlink:to="loc_srt_RangeMember_019ff61f-a835-7bcf-b443-740a9ab0ed07_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019ff61f-a835-79bf-9dce-06f96ef05985" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_019ff61f-a835-7bcf-b443-740a9ab0ed07" xlink:to="loc_srt_RangeMember_019ff61f-a835-79bf-9dce-06f96ef05985" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_019ff61f-a835-70d0-b753-88c641f626c6" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_019ff61f-a835-79bf-9dce-06f96ef05985" xlink:to="loc_srt_MaximumMember_019ff61f-a835-70d0-b753-88c641f626c6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_FuturePercentageOfRoyaltyPaymentsBasedOnNetSales_019ff61f-a835-77b8-b0ed-5bb84e507a66" xlink:href="vnda-20260930.xsd#vnda_FuturePercentageOfRoyaltyPaymentsBasedOnNetSales"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-7a46-9cca-ab7b817e6a5a" xlink:to="loc_vnda_FuturePercentageOfRoyaltyPaymentsBasedOnNetSales_019ff61f-a835-77b8-b0ed-5bb84e507a66" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_DevelopmentAndMilestoneObligationsPaidToThirdParty_019ff61f-a835-74d3-bc6c-26846a8840a6" xlink:href="vnda-20260930.xsd#vnda_DevelopmentAndMilestoneObligationsPaidToThirdParty"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-7a46-9cca-ab7b817e6a5a" xlink:to="loc_vnda_DevelopmentAndMilestoneObligationsPaidToThirdParty_019ff61f-a835-74d3-bc6c-26846a8840a6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_DevelopmentAndMilestonePaymentsPotentiallyDueToThirdParty_019ff61f-a835-7a03-a346-0694890b766d" xlink:href="vnda-20260930.xsd#vnda_DevelopmentAndMilestonePaymentsPotentiallyDueToThirdParty"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-7a46-9cca-ab7b817e6a5a" xlink:to="loc_vnda_DevelopmentAndMilestonePaymentsPotentiallyDueToThirdParty_019ff61f-a835-7a03-a346-0694890b766d" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/CommitmentsandContingenciesVQW765NarrativeDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#CommitmentsandContingenciesVQW765NarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/CommitmentsandContingenciesVQW765NarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-7b70-b8a7-3898a0b8c237" xlink:href="vnda-20260930.xsd#vnda_CommitmentsAndContingenciesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a835-79ba-b521-b5fa24f48c1a" xlink:href="vnda-20260930.xsd#vnda_CommitmentsAndContingenciesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-7b70-b8a7-3898a0b8c237" xlink:to="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a835-79ba-b521-b5fa24f48c1a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_019ff61f-a835-7f6b-a3d6-5e3f12b638ca" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a835-79ba-b521-b5fa24f48c1a" xlink:to="loc_us-gaap_TypeOfArrangementAxis_019ff61f-a835-7f6b-a3d6-5e3f12b638ca" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019ff61f-a835-7f6b-a3d6-5e3f12b638ca_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_019ff61f-a835-7f6b-a3d6-5e3f12b638ca" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019ff61f-a835-7f6b-a3d6-5e3f12b638ca_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019ff61f-a835-707b-8dd3-56f9df1e6b1a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_019ff61f-a835-7f6b-a3d6-5e3f12b638ca" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019ff61f-a835-707b-8dd3-56f9df1e6b1a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_VQW765Member_019ff61f-a835-7619-8ef0-78dc6ddcf4b9" xlink:href="vnda-20260930.xsd#vnda_VQW765Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019ff61f-a835-707b-8dd3-56f9df1e6b1a" xlink:to="loc_vnda_VQW765Member_019ff61f-a835-7619-8ef0-78dc6ddcf4b9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_FuturePercentageOfRoyaltyPaymentsBasedOnNetSales_019ff61f-a835-70ea-ac99-fd1c4ccd74cc" xlink:href="vnda-20260930.xsd#vnda_FuturePercentageOfRoyaltyPaymentsBasedOnNetSales"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-7b70-b8a7-3898a0b8c237" xlink:to="loc_vnda_FuturePercentageOfRoyaltyPaymentsBasedOnNetSales_019ff61f-a835-70ea-ac99-fd1c4ccd74cc" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/CommitmentsandContingenciesOtherAgreementsNarrativeDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#CommitmentsandContingenciesOtherAgreementsNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/CommitmentsandContingenciesOtherAgreementsNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-705f-9f94-e0621591e7d2" xlink:href="vnda-20260930.xsd#vnda_CommitmentsAndContingenciesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a835-7e3d-834f-6685be5d2ac7" xlink:href="vnda-20260930.xsd#vnda_CommitmentsAndContingenciesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-705f-9f94-e0621591e7d2" xlink:to="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a835-7e3d-834f-6685be5d2ac7" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_019ff61f-a835-7093-9ebe-9677223d93f3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_CommitmentsAndContingenciesTable_019ff61f-a835-7e3d-834f-6685be5d2ac7" xlink:to="loc_us-gaap_TypeOfArrangementAxis_019ff61f-a835-7093-9ebe-9677223d93f3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019ff61f-a835-7093-9ebe-9677223d93f3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_019ff61f-a835-7093-9ebe-9677223d93f3" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019ff61f-a835-7093-9ebe-9677223d93f3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019ff61f-a835-7e3a-9996-44ddd64efc37" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_019ff61f-a835-7093-9ebe-9677223d93f3" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019ff61f-a835-7e3a-9996-44ddd64efc37" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementTransactionWithPartyToCollaborativeArrangementMember_019ff61f-a835-7572-a371-4189d2ecd8e4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CollaborativeArrangementTransactionWithPartyToCollaborativeArrangementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019ff61f-a835-7e3a-9996-44ddd64efc37" xlink:to="loc_us-gaap_CollaborativeArrangementTransactionWithPartyToCollaborativeArrangementMember_019ff61f-a835-7572-a371-4189d2ecd8e4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_019ff61f-a835-7b05-913b-746ad861c704" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-705f-9f94-e0621591e7d2" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_019ff61f-a835-7b05-913b-746ad861c704" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ResearchAndDevelopmentExpenseReimbursableAmount_019ff61f-a835-7135-9ed0-5b5a186891e8" xlink:href="vnda-20260930.xsd#vnda_ResearchAndDevelopmentExpenseReimbursableAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-705f-9f94-e0621591e7d2" xlink:to="loc_vnda_ResearchAndDevelopmentExpenseReimbursableAmount_019ff61f-a835-7135-9ed0-5b5a186891e8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseRenewalTerm_019ff61f-a835-7425-8a91-e637248a2974" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LesseeOperatingLeaseRenewalTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-705f-9f94-e0621591e7d2" xlink:to="loc_us-gaap_LesseeOperatingLeaseRenewalTerm_019ff61f-a835-7425-8a91-e637248a2974" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability_019ff61f-a835-79b5-9370-e0676c9c07a1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-705f-9f94-e0621591e7d2" xlink:to="loc_us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability_019ff61f-a835-79b5-9370-e0676c9c07a1" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeFinanceLeaseTermOfContract1_019ff61f-a835-74b3-bf64-a71713e8f671" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LesseeFinanceLeaseTermOfContract1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-705f-9f94-e0621591e7d2" xlink:to="loc_us-gaap_LesseeFinanceLeaseTermOfContract1_019ff61f-a835-74b3-bf64-a71713e8f671" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RightOfUseAssetObtainedInExchangeForFinanceLeaseLiability_019ff61f-a835-7795-b7a3-4e9feacb6b22" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RightOfUseAssetObtainedInExchangeForFinanceLeaseLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-705f-9f94-e0621591e7d2" xlink:to="loc_us-gaap_RightOfUseAssetObtainedInExchangeForFinanceLeaseLiability_019ff61f-a835-7795-b7a3-4e9feacb6b22" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnrecordedUnconditionalPurchaseObligationBalanceSheetAmount_019ff61f-a835-776e-b9fa-f59caed46639" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_UnrecordedUnconditionalPurchaseObligationBalanceSheetAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-705f-9f94-e0621591e7d2" xlink:to="loc_us-gaap_UnrecordedUnconditionalPurchaseObligationBalanceSheetAmount_019ff61f-a835-776e-b9fa-f59caed46639" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnrecordedUnconditionalPurchaseObligationTerm_019ff61f-a835-7f63-b611-788e5e644a4d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_UnrecordedUnconditionalPurchaseObligationTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_CommitmentsAndContingenciesLineItems_019ff61f-a835-705f-9f94-e0621591e7d2" xlink:to="loc_us-gaap_UnrecordedUnconditionalPurchaseObligationTerm_019ff61f-a835-7f63-b611-788e5e644a4d" xlink:type="arc" order="7"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/StockBasedCompensationNarrativeDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#StockBasedCompensationNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/StockBasedCompensationNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-77b6-be20-b5f3fb9753be" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019ff61f-a835-7686-91a5-29a2d9d4cb59" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-77b6-be20-b5f3fb9753be" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019ff61f-a835-7686-91a5-29a2d9d4cb59" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_019ff61f-a835-71b5-ae5b-0a9849bf9ddc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019ff61f-a835-7686-91a5-29a2d9d4cb59" xlink:to="loc_us-gaap_PlanNameAxis_019ff61f-a835-71b5-ae5b-0a9849bf9ddc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019ff61f-a835-71b5-ae5b-0a9849bf9ddc_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_019ff61f-a835-71b5-ae5b-0a9849bf9ddc" xlink:to="loc_us-gaap_PlanNameDomain_019ff61f-a835-71b5-ae5b-0a9849bf9ddc_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019ff61f-a835-733b-8d07-11804cd3e011" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_019ff61f-a835-71b5-ae5b-0a9849bf9ddc" xlink:to="loc_us-gaap_PlanNameDomain_019ff61f-a835-733b-8d07-11804cd3e011" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_TwoThousandSixPlanAndTwoThousandSixteenPlanMember_019ff61f-a835-7bb9-af46-d19fb81676f2" xlink:href="vnda-20260930.xsd#vnda_TwoThousandSixPlanAndTwoThousandSixteenPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_019ff61f-a835-733b-8d07-11804cd3e011" xlink:to="loc_vnda_TwoThousandSixPlanAndTwoThousandSixteenPlanMember_019ff61f-a835-7bb9-af46-d19fb81676f2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_TwoThousandSixteenPlanMember_019ff61f-a835-7032-a2f6-7f81e9de6fb7" xlink:href="vnda-20260930.xsd#vnda_TwoThousandSixteenPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_TwoThousandSixPlanAndTwoThousandSixteenPlanMember_019ff61f-a835-7bb9-af46-d19fb81676f2" xlink:to="loc_vnda_TwoThousandSixteenPlanMember_019ff61f-a835-7032-a2f6-7f81e9de6fb7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsRestrictedStockUnitsAndPerformanceRestrictedStockUnitsOutstandingNumber_019ff61f-a835-7968-b4f1-ec797fb9dfe8" xlink:href="vnda-20260930.xsd#vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsRestrictedStockUnitsAndPerformanceRestrictedStockUnitsOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-77b6-be20-b5f3fb9753be" xlink:to="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsRestrictedStockUnitsAndPerformanceRestrictedStockUnitsOutstandingNumber_019ff61f-a835-7968-b4f1-ec797fb9dfe8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_019ff61f-a835-7f2f-ac5e-47793a510f29" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-77b6-be20-b5f3fb9753be" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_019ff61f-a835-7f2f-ac5e-47793a510f29" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_019ff61f-a835-7280-8b7b-48afc51dca9c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-77b6-be20-b5f3fb9753be" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_019ff61f-a835-7280-8b7b-48afc51dca9c" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/StockBasedCompensationStockOptionNarrativeDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#StockBasedCompensationStockOptionNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/StockBasedCompensationStockOptionNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-7edc-8842-439534b97f87" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019ff61f-a835-7506-91df-116a66067d54" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-7edc-8842-439534b97f87" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019ff61f-a835-7506-91df-116a66067d54" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019ff61f-a835-73b7-9b4a-4ec70c1fd06c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019ff61f-a835-7506-91df-116a66067d54" xlink:to="loc_us-gaap_AwardTypeAxis_019ff61f-a835-73b7-9b4a-4ec70c1fd06c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-73b7-9b4a-4ec70c1fd06c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019ff61f-a835-73b7-9b4a-4ec70c1fd06c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-73b7-9b4a-4ec70c1fd06c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-72a6-95df-310f2ff4b742" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019ff61f-a835-73b7-9b4a-4ec70c1fd06c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-72a6-95df-310f2ff4b742" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ServiceOptionAwardsMember_019ff61f-a835-7872-ae62-94424212a739" xlink:href="vnda-20260930.xsd#vnda_ServiceOptionAwardsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-72a6-95df-310f2ff4b742" xlink:to="loc_vnda_ServiceOptionAwardsMember_019ff61f-a835-7872-ae62-94424212a739" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ShareBasedCompensationOptionAwardsContractualTerm_019ff61f-a835-74ca-9ba7-c29bd8defb0a" xlink:href="vnda-20260930.xsd#vnda_ShareBasedCompensationOptionAwardsContractualTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-7edc-8842-439534b97f87" xlink:to="loc_vnda_ShareBasedCompensationOptionAwardsContractualTerm_019ff61f-a835-74ca-9ba7-c29bd8defb0a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAnnualAwardVestingPeriodEmployeesAndNewDirectors_019ff61f-a835-7fd5-af9d-abcf9167a19e" xlink:href="vnda-20260930.xsd#vnda_ShareBasedCompensationArrangementByShareBasedPaymentAnnualAwardVestingPeriodEmployeesAndNewDirectors"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-7edc-8842-439534b97f87" xlink:to="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAnnualAwardVestingPeriodEmployeesAndNewDirectors_019ff61f-a835-7fd5-af9d-abcf9167a19e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfShareSubjectToOptionAwards_019ff61f-a835-7442-af02-60dfbc20cec4" xlink:href="vnda-20260930.xsd#vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfShareSubjectToOptionAwards"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-7edc-8842-439534b97f87" xlink:to="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfShareSubjectToOptionAwards_019ff61f-a835-7442-af02-60dfbc20cec4" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardRemainingPercentageOfShareSubjectToOptionAwards_019ff61f-a835-7f19-a6af-a3ef92d9ce3a" xlink:href="vnda-20260930.xsd#vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardRemainingPercentageOfShareSubjectToOptionAwards"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-7edc-8842-439534b97f87" xlink:to="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardRemainingPercentageOfShareSubjectToOptionAwards_019ff61f-a835-7f19-a6af-a3ef92d9ce3a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_SharebasedCompensationArrangementbyShareBasedPaymentAwardOptionsVestingPeriodNumberOfEqualMonthlyInstallments_019ff61f-a835-782a-976b-1edcf6706a2d" xlink:href="vnda-20260930.xsd#vnda_SharebasedCompensationArrangementbyShareBasedPaymentAwardOptionsVestingPeriodNumberOfEqualMonthlyInstallments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-7edc-8842-439534b97f87" xlink:to="loc_vnda_SharebasedCompensationArrangementbyShareBasedPaymentAwardOptionsVestingPeriodNumberOfEqualMonthlyInstallments_019ff61f-a835-782a-976b-1edcf6706a2d" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardAcceleratedVestingInvoluntaryTerminationPeriodAfterChangeInControl_019ff61f-a835-70f9-86f1-a3413ba06120" xlink:href="vnda-20260930.xsd#vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardAcceleratedVestingInvoluntaryTerminationPeriodAfterChangeInControl"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-7edc-8842-439534b97f87" xlink:to="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardAcceleratedVestingInvoluntaryTerminationPeriodAfterChangeInControl_019ff61f-a835-70f9-86f1-a3413ba06120" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_019ff61f-a835-70dd-a18e-6d1037a70eed" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-7edc-8842-439534b97f87" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_019ff61f-a835-70dd-a18e-6d1037a70eed" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_019ff61f-a835-75b0-b556-a9eec2bcffd1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-7edc-8842-439534b97f87" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_019ff61f-a835-75b0-b556-a9eec2bcffd1" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_019ff61f-a835-7686-8849-8787b017af4f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-7edc-8842-439534b97f87" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_019ff61f-a835-7686-8849-8787b017af4f" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_019ff61f-a835-7dfb-bf42-b5658a6ae052" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-7edc-8842-439534b97f87" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_019ff61f-a835-7dfb-bf42-b5658a6ae052" xlink:type="arc" order="9"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/StockBasedCompensationScheduleofOptionActivityDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#StockBasedCompensationScheduleofOptionActivityDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/StockBasedCompensationScheduleofOptionActivityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-76bf-bfe4-c3e3590cd7da" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019ff61f-a835-770a-920f-3f8ea90e0860" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-76bf-bfe4-c3e3590cd7da" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019ff61f-a835-770a-920f-3f8ea90e0860" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_019ff61f-a835-7048-bfba-fdcefdba114c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019ff61f-a835-770a-920f-3f8ea90e0860" xlink:to="loc_us-gaap_PlanNameAxis_019ff61f-a835-7048-bfba-fdcefdba114c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019ff61f-a835-7048-bfba-fdcefdba114c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_019ff61f-a835-7048-bfba-fdcefdba114c" xlink:to="loc_us-gaap_PlanNameDomain_019ff61f-a835-7048-bfba-fdcefdba114c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019ff61f-a835-7b34-9da0-50aee3a206fc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_019ff61f-a835-7048-bfba-fdcefdba114c" xlink:to="loc_us-gaap_PlanNameDomain_019ff61f-a835-7b34-9da0-50aee3a206fc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_TwoThousandSixPlanAndTwoThousandSixteenPlanMember_019ff61f-a835-70ea-afde-45686106e116" xlink:href="vnda-20260930.xsd#vnda_TwoThousandSixPlanAndTwoThousandSixteenPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_019ff61f-a835-7b34-9da0-50aee3a206fc" xlink:to="loc_vnda_TwoThousandSixPlanAndTwoThousandSixteenPlanMember_019ff61f-a835-70ea-afde-45686106e116" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_019ff61f-a835-74da-97f8-5a7e8701005e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-76bf-bfe4-c3e3590cd7da" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_019ff61f-a835-74da-97f8-5a7e8701005e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_019ff61f-a835-7f0c-a4aa-bd57c7ad6be2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_019ff61f-a835-74da-97f8-5a7e8701005e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_019ff61f-a835-7f0c-a4aa-bd57c7ad6be2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod_019ff61f-a835-7ca9-8927-bff063a03968" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_019ff61f-a835-74da-97f8-5a7e8701005e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod_019ff61f-a835-7ca9-8927-bff063a03968" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExpirationsInPeriod_019ff61f-a835-7e0b-8001-ee21df543b3b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExpirationsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_019ff61f-a835-74da-97f8-5a7e8701005e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExpirationsInPeriod_019ff61f-a835-7e0b-8001-ee21df543b3b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_019ff61f-a835-75f5-80d0-dd1b9f684725" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber_019ff61f-a835-7e6e-97c0-5d5bb9a228aa" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-76bf-bfe4-c3e3590cd7da" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber_019ff61f-a835-7e6e-97c0-5d5bb9a228aa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber_019ff61f-a835-7197-a11e-aec15572cbfd" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-76bf-bfe4-c3e3590cd7da" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber_019ff61f-a835-7197-a11e-aec15572cbfd" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_019ff61f-a835-744d-ad97-42176bf51a0d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-76bf-bfe4-c3e3590cd7da" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_019ff61f-a835-744d-ad97-42176bf51a0d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_019ff61f-a835-7cf5-be7a-502b4a6a8e74" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_019ff61f-a835-744d-ad97-42176bf51a0d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_019ff61f-a835-7cf5-be7a-502b4a6a8e74" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice_019ff61f-a835-7940-a46c-2c07549ee62c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_019ff61f-a835-744d-ad97-42176bf51a0d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice_019ff61f-a835-7940-a46c-2c07549ee62c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExpirationsInPeriodWeightedAverageExercisePrice_019ff61f-a835-779a-8351-7553f7976ff4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExpirationsInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_019ff61f-a835-744d-ad97-42176bf51a0d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExpirationsInPeriodWeightedAverageExercisePrice_019ff61f-a835-779a-8351-7553f7976ff4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_019ff61f-a835-7626-9088-2e0fe062ef02" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice_019ff61f-a835-7c47-a32b-9ed8c049a0f7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-76bf-bfe4-c3e3590cd7da" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice_019ff61f-a835-7c47-a32b-9ed8c049a0f7" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice_019ff61f-a835-78fd-9d80-0440500f82e1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-76bf-bfe4-c3e3590cd7da" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice_019ff61f-a835-78fd-9d80-0440500f82e1" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTermAbstract_019ff61f-a835-7e96-9945-4601e217918b" xlink:href="vnda-20260930.xsd#vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTermAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-76bf-bfe4-c3e3590cd7da" xlink:to="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTermAbstract_019ff61f-a835-7e96-9945-4601e217918b" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2_019ff61f-a835-7a86-9edb-bba36a3b251f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTermAbstract_019ff61f-a835-7e96-9945-4601e217918b" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2_019ff61f-a835-7a86-9edb-bba36a3b251f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1_019ff61f-a835-7398-9c47-56ddac8de2dc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTermAbstract_019ff61f-a835-7e96-9945-4601e217918b" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1_019ff61f-a835-7398-9c47-56ddac8de2dc" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1_019ff61f-a835-70c4-b8e9-a67a95a8cb37" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-76bf-bfe4-c3e3590cd7da" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1_019ff61f-a835-70c4-b8e9-a67a95a8cb37" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_019ff61f-a835-7f6c-ad9a-57eda8de7f23" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-76bf-bfe4-c3e3590cd7da" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_019ff61f-a835-7f6c-ad9a-57eda8de7f23" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_019ff61f-a835-7adb-b36d-126cf93e7059" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_019ff61f-a835-7f6c-ad9a-57eda8de7f23" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_019ff61f-a835-7adb-b36d-126cf93e7059" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1_019ff61f-a835-73d7-acf3-215cc22c3657" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-76bf-bfe4-c3e3590cd7da" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1_019ff61f-a835-73d7-acf3-215cc22c3657" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue_019ff61f-a835-75f6-b0d1-0dfbb10a08c0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-76bf-bfe4-c3e3590cd7da" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue_019ff61f-a835-75f6-b0d1-0dfbb10a08c0" xlink:type="arc" order="10"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/StockBasedCompensationRestrictedStockUnitsNarrativeDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#StockBasedCompensationRestrictedStockUnitsNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/StockBasedCompensationRestrictedStockUnitsNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-734f-8ddf-aa7b15c5b86b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019ff61f-a835-71c3-af83-85ac05f48298" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-734f-8ddf-aa7b15c5b86b" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019ff61f-a835-71c3-af83-85ac05f48298" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019ff61f-a835-792c-bf9d-fa6bc4fc5478" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019ff61f-a835-71c3-af83-85ac05f48298" xlink:to="loc_us-gaap_AwardTypeAxis_019ff61f-a835-792c-bf9d-fa6bc4fc5478" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-792c-bf9d-fa6bc4fc5478_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019ff61f-a835-792c-bf9d-fa6bc4fc5478" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-792c-bf9d-fa6bc4fc5478_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-77fe-834a-590ebaa9bea8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019ff61f-a835-792c-bf9d-fa6bc4fc5478" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-77fe-834a-590ebaa9bea8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_019ff61f-a835-760a-a5cc-6f1d1130fc5a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-77fe-834a-590ebaa9bea8" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_019ff61f-a835-760a-a5cc-6f1d1130fc5a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_SharebasedCompensationArrangementbyShareBasedPaymentAwardOptionsVestingPeriodNumberOfEqualMonthlyInstallments_019ff61f-a835-7e3e-bcc8-556cda8e5905" xlink:href="vnda-20260930.xsd#vnda_SharebasedCompensationArrangementbyShareBasedPaymentAwardOptionsVestingPeriodNumberOfEqualMonthlyInstallments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-734f-8ddf-aa7b15c5b86b" xlink:to="loc_vnda_SharebasedCompensationArrangementbyShareBasedPaymentAwardOptionsVestingPeriodNumberOfEqualMonthlyInstallments_019ff61f-a835-7e3e-bcc8-556cda8e5905" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardAcceleratedVestingInvoluntaryTerminationPeriodAfterChangeInControl_019ff61f-a835-780a-ae32-b031821080b3" xlink:href="vnda-20260930.xsd#vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardAcceleratedVestingInvoluntaryTerminationPeriodAfterChangeInControl"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-734f-8ddf-aa7b15c5b86b" xlink:to="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardAcceleratedVestingInvoluntaryTerminationPeriodAfterChangeInControl_019ff61f-a835-780a-ae32-b031821080b3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_019ff61f-a835-754d-ae63-f45006e22344" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-734f-8ddf-aa7b15c5b86b" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_019ff61f-a835-754d-ae63-f45006e22344" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_019ff61f-a835-70ef-aa14-6a9bd31bf7b3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-734f-8ddf-aa7b15c5b86b" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_019ff61f-a835-70ef-aa14-6a9bd31bf7b3" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_019ff61f-a835-74b1-9c7f-ac104dc0ad06" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-734f-8ddf-aa7b15c5b86b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_019ff61f-a835-74b1-9c7f-ac104dc0ad06" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodTotalFairValue_019ff61f-a835-7c11-88a6-bf3181d4488b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodTotalFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019ff61f-a835-734f-8ddf-aa7b15c5b86b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodTotalFairValue_019ff61f-a835-7c11-88a6-bf3181d4488b" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/StockBasedCompensationScheduleofRSUActivityDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#StockBasedCompensationScheduleofRSUActivityDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/StockBasedCompensationScheduleofRSUActivityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsLineItems_019ff61f-a835-70ee-bcc8-a3f288ab9efc" xlink:href="vnda-20260930.xsd#vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsTable_019ff61f-a835-73df-8822-f699a2116b32" xlink:href="vnda-20260930.xsd#vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsLineItems_019ff61f-a835-70ee-bcc8-a3f288ab9efc" xlink:to="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsTable_019ff61f-a835-73df-8822-f699a2116b32" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019ff61f-a835-709a-81f3-531a1052113c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsTable_019ff61f-a835-73df-8822-f699a2116b32" xlink:to="loc_us-gaap_AwardTypeAxis_019ff61f-a835-709a-81f3-531a1052113c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-709a-81f3-531a1052113c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019ff61f-a835-709a-81f3-531a1052113c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-709a-81f3-531a1052113c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-70db-9e67-c516d942796b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019ff61f-a835-709a-81f3-531a1052113c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-70db-9e67-c516d942796b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_019ff61f-a835-7c4b-b0c9-98cc0343dbf9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-70db-9e67-c516d942796b" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_019ff61f-a835-7c4b-b0c9-98cc0343dbf9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019ff61f-a835-7df2-b2f2-e3f6e455b4d5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsLineItems_019ff61f-a835-70ee-bcc8-a3f288ab9efc" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019ff61f-a835-7df2-b2f2-e3f6e455b4d5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_019ff61f-a835-78f6-907d-1097ed5378ec" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019ff61f-a835-7df2-b2f2-e3f6e455b4d5" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_019ff61f-a835-78f6-907d-1097ed5378ec" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_019ff61f-a835-763a-9c49-383bfcf8dc43" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019ff61f-a835-7df2-b2f2-e3f6e455b4d5" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_019ff61f-a835-763a-9c49-383bfcf8dc43" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_019ff61f-a835-7051-acd2-25f76d8f9eb5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019ff61f-a835-7df2-b2f2-e3f6e455b4d5" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_019ff61f-a835-7051-acd2-25f76d8f9eb5" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_019ff61f-a835-741b-90ef-46c24cf3131b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019ff61f-a835-7df2-b2f2-e3f6e455b4d5" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_019ff61f-a835-741b-90ef-46c24cf3131b" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_019ff61f-a835-7fdc-9aa8-650d09aae811" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019ff61f-a835-73c3-ae5d-576d731c7878" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsLineItems_019ff61f-a835-70ee-bcc8-a3f288ab9efc" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019ff61f-a835-73c3-ae5d-576d731c7878" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_019ff61f-a835-7f23-a46a-392489a11901" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019ff61f-a835-73c3-ae5d-576d731c7878" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_019ff61f-a835-7f23-a46a-392489a11901" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_019ff61f-a835-722b-845c-e0be066a0b67" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019ff61f-a835-73c3-ae5d-576d731c7878" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_019ff61f-a835-722b-845c-e0be066a0b67" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_019ff61f-a835-7ef4-b257-9c7bc75117d4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019ff61f-a835-73c3-ae5d-576d731c7878" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_019ff61f-a835-7ef4-b257-9c7bc75117d4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_019ff61f-a835-7777-b6bb-0e34e768d1d1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019ff61f-a835-73c3-ae5d-576d731c7878" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_019ff61f-a835-7777-b6bb-0e34e768d1d1" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_019ff61f-a835-7552-9331-82eb3d3cfbf6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/StockBasedCompensationPerformanceRestrictedStockUnitsNarrativeDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#StockBasedCompensationPerformanceRestrictedStockUnitsNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/StockBasedCompensationPerformanceRestrictedStockUnitsNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsLineItems_019ff61f-a835-7607-a556-86df84c645a9" xlink:href="vnda-20260930.xsd#vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsTable_019ff61f-a835-7b72-a421-3d0b5c543a5a" xlink:href="vnda-20260930.xsd#vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsLineItems_019ff61f-a835-7607-a556-86df84c645a9" xlink:to="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsTable_019ff61f-a835-7b72-a421-3d0b5c543a5a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019ff61f-a835-744c-a036-803452fdb5d6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsTable_019ff61f-a835-7b72-a421-3d0b5c543a5a" xlink:to="loc_us-gaap_AwardTypeAxis_019ff61f-a835-744c-a036-803452fdb5d6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-744c-a036-803452fdb5d6_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019ff61f-a835-744c-a036-803452fdb5d6" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-744c-a036-803452fdb5d6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-7d4f-917e-a829fa209a03" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019ff61f-a835-744c-a036-803452fdb5d6" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-7d4f-917e-a829fa209a03" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PerformanceSharesMember_019ff61f-a835-746c-beac-02b7985727d1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PerformanceSharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-7d4f-917e-a829fa209a03" xlink:to="loc_us-gaap_PerformanceSharesMember_019ff61f-a835-746c-beac-02b7985727d1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_019ff61f-a835-7f4b-aac3-91995626f7dd" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsTable_019ff61f-a835-7b72-a421-3d0b5c543a5a" xlink:to="loc_srt_RangeAxis_019ff61f-a835-7f4b-aac3-91995626f7dd" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019ff61f-a835-7f4b-aac3-91995626f7dd_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_019ff61f-a835-7f4b-aac3-91995626f7dd" xlink:to="loc_srt_RangeMember_019ff61f-a835-7f4b-aac3-91995626f7dd_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019ff61f-a835-73f0-b066-14a38c1b319e" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_019ff61f-a835-7f4b-aac3-91995626f7dd" xlink:to="loc_srt_RangeMember_019ff61f-a835-73f0-b066-14a38c1b319e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_019ff61f-a835-7e8a-ade6-e081f7befc71" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_019ff61f-a835-73f0-b066-14a38c1b319e" xlink:to="loc_srt_MinimumMember_019ff61f-a835-7e8a-ade6-e081f7befc71" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_019ff61f-a835-7edc-a994-b9248d306110" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_019ff61f-a835-73f0-b066-14a38c1b319e" xlink:to="loc_srt_MaximumMember_019ff61f-a835-7edc-a994-b9248d306110" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesGrantedPercentageOfTarget_019ff61f-a835-7123-89cf-bd13574bad95" xlink:href="vnda-20260930.xsd#vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesGrantedPercentageOfTarget"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsLineItems_019ff61f-a835-7607-a556-86df84c645a9" xlink:to="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesGrantedPercentageOfTarget_019ff61f-a835-7123-89cf-bd13574bad95" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardPerformancePeriod_019ff61f-a835-7249-8381-3a00c2512e6b" xlink:href="vnda-20260930.xsd#vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardPerformancePeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsLineItems_019ff61f-a835-7607-a556-86df84c645a9" xlink:to="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardPerformancePeriod_019ff61f-a835-7249-8381-3a00c2512e6b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardAcceleratedVestingInvoluntaryTerminationPeriodAfterChangeInControl_019ff61f-a835-7cb5-8058-27155cfe9d09" xlink:href="vnda-20260930.xsd#vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardAcceleratedVestingInvoluntaryTerminationPeriodAfterChangeInControl"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsLineItems_019ff61f-a835-7607-a556-86df84c645a9" xlink:to="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardAcceleratedVestingInvoluntaryTerminationPeriodAfterChangeInControl_019ff61f-a835-7cb5-8058-27155cfe9d09" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_019ff61f-a835-7050-ae53-121da85f8a78" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsLineItems_019ff61f-a835-7607-a556-86df84c645a9" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_019ff61f-a835-7050-ae53-121da85f8a78" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_019ff61f-a835-7ff0-a658-a989316488de" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsLineItems_019ff61f-a835-7607-a556-86df84c645a9" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_019ff61f-a835-7ff0-a658-a989316488de" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_019ff61f-a835-7cea-a36b-38722d8ac9a6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsLineItems_019ff61f-a835-7607-a556-86df84c645a9" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_019ff61f-a835-7cea-a36b-38722d8ac9a6" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/StockBasedCompensationScheduleofPSUActivityDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#StockBasedCompensationScheduleofPSUActivityDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/StockBasedCompensationScheduleofPSUActivityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsLineItems_019ff61f-a835-7555-8c1f-706225142381" xlink:href="vnda-20260930.xsd#vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsTable_019ff61f-a835-7dd2-a0ef-aa2b996ad737" xlink:href="vnda-20260930.xsd#vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsLineItems_019ff61f-a835-7555-8c1f-706225142381" xlink:to="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsTable_019ff61f-a835-7dd2-a0ef-aa2b996ad737" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019ff61f-a835-7ac5-9a82-dd0cf6bcc841" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsTable_019ff61f-a835-7dd2-a0ef-aa2b996ad737" xlink:to="loc_us-gaap_AwardTypeAxis_019ff61f-a835-7ac5-9a82-dd0cf6bcc841" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-7ac5-9a82-dd0cf6bcc841_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019ff61f-a835-7ac5-9a82-dd0cf6bcc841" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-7ac5-9a82-dd0cf6bcc841_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-7e0d-9d6f-c667ba1176c6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019ff61f-a835-7ac5-9a82-dd0cf6bcc841" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-7e0d-9d6f-c667ba1176c6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PerformanceSharesMember_019ff61f-a835-7da6-92a9-57ac61b08922" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PerformanceSharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-7e0d-9d6f-c667ba1176c6" xlink:to="loc_us-gaap_PerformanceSharesMember_019ff61f-a835-7da6-92a9-57ac61b08922" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019ff61f-a835-7ff0-a2ff-b63d253a82f4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsLineItems_019ff61f-a835-7555-8c1f-706225142381" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019ff61f-a835-7ff0-a2ff-b63d253a82f4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_019ff61f-a835-739b-a744-61a1f479ce8d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019ff61f-a835-7ff0-a2ff-b63d253a82f4" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_019ff61f-a835-739b-a744-61a1f479ce8d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_019ff61f-a835-7b91-8a97-d3a3dc560e04" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019ff61f-a835-7ff0-a2ff-b63d253a82f4" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_019ff61f-a835-7b91-8a97-d3a3dc560e04" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_019ff61f-a835-741b-afbf-57e4a3103f58" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019ff61f-a835-7ff0-a2ff-b63d253a82f4" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_019ff61f-a835-741b-afbf-57e4a3103f58" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_019ff61f-a835-776d-8fef-288cbc1cda06" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019ff61f-a835-769b-ab8c-41e758b912eb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_vnda_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsRestrictedStockUnitsLineItems_019ff61f-a835-7555-8c1f-706225142381" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019ff61f-a835-769b-ab8c-41e758b912eb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_019ff61f-a835-7791-bbb8-fdce3883be2e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019ff61f-a835-769b-ab8c-41e758b912eb" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_019ff61f-a835-7791-bbb8-fdce3883be2e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_019ff61f-a835-771c-a7ab-b1e8fe03292d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019ff61f-a835-769b-ab8c-41e758b912eb" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_019ff61f-a835-771c-a7ab-b1e8fe03292d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_019ff61f-a835-741d-afe2-d62b0d5ac04e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019ff61f-a835-769b-ab8c-41e758b912eb" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_019ff61f-a835-741d-afe2-d62b0d5ac04e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_019ff61f-a835-76b8-9685-d08d5d5666c6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/StockBasedCompensationScheduleofStockBasedCompensationExpenseDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#StockBasedCompensationScheduleofStockBasedCompensationExpenseDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/StockBasedCompensationScheduleofStockBasedCompensationExpenseDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019ff61f-a835-75b5-8775-479c6bc7a3bc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019ff61f-a835-72b4-a7f5-e41b02bf4982" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019ff61f-a835-75b5-8775-479c6bc7a3bc" xlink:to="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019ff61f-a835-72b4-a7f5-e41b02bf4982" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_019ff61f-a835-7bc8-b5ea-a56e6b3a6298" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019ff61f-a835-72b4-a7f5-e41b02bf4982" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_019ff61f-a835-7bc8-b5ea-a56e6b3a6298" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_019ff61f-a835-7bc8-b5ea-a56e6b3a6298_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_019ff61f-a835-7bc8-b5ea-a56e6b3a6298" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_019ff61f-a835-7bc8-b5ea-a56e6b3a6298_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_019ff61f-a835-712e-8b7d-dac04d447ddd" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_019ff61f-a835-7bc8-b5ea-a56e6b3a6298" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_019ff61f-a835-712e-8b7d-dac04d447ddd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseMember_019ff61f-a835-7761-bf16-1980401fd96d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_019ff61f-a835-712e-8b7d-dac04d447ddd" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseMember_019ff61f-a835-7761-bf16-1980401fd96d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpensesMember_019ff61f-a835-7d17-874f-905c4f2e493a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SellingGeneralAndAdministrativeExpensesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_019ff61f-a835-712e-8b7d-dac04d447ddd" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpensesMember_019ff61f-a835-7d17-874f-905c4f2e493a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_019ff61f-a835-776c-9657-0787b0a6ae86" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019ff61f-a835-75b5-8775-479c6bc7a3bc" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_019ff61f-a835-776c-9657-0787b0a6ae86" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/StockBasedCompensationStockBasedCompensationExpenseNarrativeDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#StockBasedCompensationStockBasedCompensationExpenseNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/StockBasedCompensationStockBasedCompensationExpenseNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019ff61f-a835-74d7-9e98-19b5813eafbb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019ff61f-a835-7f75-922c-b595e53b7165" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019ff61f-a835-74d7-9e98-19b5813eafbb" xlink:to="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019ff61f-a835-7f75-922c-b595e53b7165" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019ff61f-a835-70a0-b559-e8627950ebce" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019ff61f-a835-7f75-922c-b595e53b7165" xlink:to="loc_us-gaap_AwardTypeAxis_019ff61f-a835-70a0-b559-e8627950ebce" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-70a0-b559-e8627950ebce_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019ff61f-a835-70a0-b559-e8627950ebce" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-70a0-b559-e8627950ebce_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-7c7c-bf99-ac5c72889cfb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019ff61f-a835-70a0-b559-e8627950ebce" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-7c7c-bf99-ac5c72889cfb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PerformanceSharesMember_019ff61f-a835-7c86-864e-a855f341434d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PerformanceSharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-7c7c-bf99-ac5c72889cfb" xlink:to="loc_us-gaap_PerformanceSharesMember_019ff61f-a835-7c86-864e-a855f341434d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_019ff61f-a835-7c09-844e-786b45574b7a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019ff61f-a835-74d7-9e98-19b5813eafbb" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_019ff61f-a835-7c09-844e-786b45574b7a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_019ff61f-a835-7c45-b7a1-7e64cc2be6b4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019ff61f-a835-74d7-9e98-19b5813eafbb" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_019ff61f-a835-7c45-b7a1-7e64cc2be6b4" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/StockBasedCompensationScheduleofMoteCarloModelforPSUsGrantedDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#StockBasedCompensationScheduleofMoteCarloModelforPSUsGrantedDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/StockBasedCompensationScheduleofMoteCarloModelforPSUsGrantedDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019ff61f-a835-7850-a5f8-a9135d8a0f94" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019ff61f-a835-7f3f-97cf-fb9a07332ef7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019ff61f-a835-7850-a5f8-a9135d8a0f94" xlink:to="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019ff61f-a835-7f3f-97cf-fb9a07332ef7" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019ff61f-a835-7e75-8a9a-a3169ee7cb49" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019ff61f-a835-7f3f-97cf-fb9a07332ef7" xlink:to="loc_us-gaap_AwardTypeAxis_019ff61f-a835-7e75-8a9a-a3169ee7cb49" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-7e75-8a9a-a3169ee7cb49_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019ff61f-a835-7e75-8a9a-a3169ee7cb49" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-7e75-8a9a-a3169ee7cb49_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-7dfe-bebf-6c16463d28f6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019ff61f-a835-7e75-8a9a-a3169ee7cb49" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-7dfe-bebf-6c16463d28f6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PerformanceSharesMember_019ff61f-a835-7870-93bc-06cf88ed25d3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PerformanceSharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019ff61f-a835-7dfe-bebf-6c16463d28f6" xlink:to="loc_us-gaap_PerformanceSharesMember_019ff61f-a835-7870-93bc-06cf88ed25d3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_019ff61f-a835-7f1e-a812-7236a032efb9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019ff61f-a835-7850-a5f8-a9135d8a0f94" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_019ff61f-a835-7f1e-a812-7236a032efb9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate_019ff61f-a835-7b2f-97dd-90b11aad4340" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019ff61f-a835-7850-a5f8-a9135d8a0f94" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate_019ff61f-a835-7b2f-97dd-90b11aad4340" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRemainingPerformancePeriod_019ff61f-a835-76c9-9c47-21829cd7891b" xlink:href="vnda-20260930.xsd#vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRemainingPerformancePeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019ff61f-a835-7850-a5f8-a9135d8a0f94" xlink:to="loc_vnda_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRemainingPerformancePeriod_019ff61f-a835-76c9-9c47-21829cd7891b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_019ff61f-a835-7454-af36-75bf632413c4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019ff61f-a835-7850-a5f8-a9135d8a0f94" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_019ff61f-a835-7454-af36-75bf632413c4" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.vandapharmaceuticals.com/role/SegmentsScheduleofSegmentRevenueandSignificantExpensesDetails" xlink:type="simple" xlink:href="vnda-20260930.xsd#SegmentsScheduleofSegmentRevenueandSignificantExpensesDetails"/>
  <link:definitionLink xlink:role="http://www.vandapharmaceuticals.com/role/SegmentsScheduleofSegmentRevenueandSignificantExpensesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingRevenueReconcilingItemLineItems_019ff61f-a835-7e31-bea0-48235d2a5813" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentReportingRevenueReconcilingItemLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReconciliationOfRevenueFromSegmentsToConsolidatedTable_019ff61f-a835-7be9-914e-4cc1fb656c75" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ReconciliationOfRevenueFromSegmentsToConsolidatedTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SegmentReportingRevenueReconcilingItemLineItems_019ff61f-a835-7e31-bea0-48235d2a5813" xlink:to="loc_us-gaap_ReconciliationOfRevenueFromSegmentsToConsolidatedTable_019ff61f-a835-7be9-914e-4cc1fb656c75" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementBusinessSegmentsAxis_019ff61f-a835-70fa-8204-9937e8d9d2c0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementBusinessSegmentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ReconciliationOfRevenueFromSegmentsToConsolidatedTable_019ff61f-a835-7be9-914e-4cc1fb656c75" xlink:to="loc_us-gaap_StatementBusinessSegmentsAxis_019ff61f-a835-70fa-8204-9937e8d9d2c0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_019ff61f-a835-70fa-8204-9937e8d9d2c0_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_019ff61f-a835-70fa-8204-9937e8d9d2c0" xlink:to="loc_us-gaap_SegmentDomain_019ff61f-a835-70fa-8204-9937e8d9d2c0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_019ff61f-a835-78ef-87cc-6f1653db9a68" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_019ff61f-a835-70fa-8204-9937e8d9d2c0" xlink:to="loc_us-gaap_SegmentDomain_019ff61f-a835-78ef-87cc-6f1653db9a68" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_vnda_ProductSegmentsMember_019ff61f-a835-73f0-a8f1-f203e8399bc1" xlink:href="vnda-20260930.xsd#vnda_ProductSegmentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentDomain_019ff61f-a835-78ef-87cc-6f1653db9a68" xlink:to="loc_vnda_ProductSegmentsMember_019ff61f-a835-73f0-a8f1-f203e8399bc1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_019ff61f-a835-70a8-aa05-e12ba4418dea" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingRevenueReconcilingItemLineItems_019ff61f-a835-7e31-bea0-48235d2a5813" xlink:to="loc_us-gaap_Revenues_019ff61f-a835-70a8-aa05-e12ba4418dea" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServiceExcludingDepreciationDepletionAndAmortization_019ff61f-a835-72bf-a51e-663142be2c8a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CostOfGoodsAndServiceExcludingDepreciationDepletionAndAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingRevenueReconcilingItemLineItems_019ff61f-a835-7e31-bea0-48235d2a5813" xlink:to="loc_us-gaap_CostOfGoodsAndServiceExcludingDepreciationDepletionAndAmortization_019ff61f-a835-72bf-a51e-663142be2c8a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_019ff61f-a835-732f-a45f-5a47c960c602" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingRevenueReconcilingItemLineItems_019ff61f-a835-7e31-bea0-48235d2a5813" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_019ff61f-a835-732f-a45f-5a47c960c602" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpense_019ff61f-a835-7734-8ddb-abcf1c82e2ed" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SellingGeneralAndAdministrativeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingRevenueReconcilingItemLineItems_019ff61f-a835-7e31-bea0-48235d2a5813" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpense_019ff61f-a835-7734-8ddb-abcf1c82e2ed" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfIntangibleAssets_019ff61f-a835-7e0f-bf8f-23e7afeb48ee" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AmortizationOfIntangibleAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingRevenueReconcilingItemLineItems_019ff61f-a835-7e31-bea0-48235d2a5813" xlink:to="loc_us-gaap_AmortizationOfIntangibleAssets_019ff61f-a835-7e0f-bf8f-23e7afeb48ee" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherIncome_019ff61f-a835-70eb-bb80-e6f12937513a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherIncome"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingRevenueReconcilingItemLineItems_019ff61f-a835-7e31-bea0-48235d2a5813" xlink:to="loc_us-gaap_OtherIncome_019ff61f-a835-70eb-bb80-e6f12937513a" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_019ff61f-a835-79eb-a9c0-085aa41fa7ac" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingRevenueReconcilingItemLineItems_019ff61f-a835-7e31-bea0-48235d2a5813" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_019ff61f-a835-79eb-a9c0-085aa41fa7ac" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_019ff61f-a835-787a-947e-e7b1e5938806" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingRevenueReconcilingItemLineItems_019ff61f-a835-7e31-bea0-48235d2a5813" xlink:to="loc_us-gaap_NetIncomeLoss_019ff61f-a835-787a-947e-e7b1e5938806" xlink:type="arc" order="7"/>
  </link:definitionLink>
</link:linkbase>
