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

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2026 Workiva-->
<!--r:019fd051-c20c-7019-8ae4-4b0ac88d6af5,g:8b196b36-3837-45e6-879d-e9efa671d6e9-->
<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.penumbrainc.com/role/CondensedConsolidatedStatementsofStockholdersEquity" xlink:type="simple" xlink:href="pen-20260930.xsd#CondensedConsolidatedStatementsofStockholdersEquity"/>
  <link:definitionLink xlink:role="http://www.penumbrainc.com/role/CondensedConsolidatedStatementsofStockholdersEquity" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_019fd051-c358-7114-a99a-5e7fdd16c060" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_019fd051-c358-7bbd-a1e3-9ecb7e132963" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_019fd051-c358-7114-a99a-5e7fdd16c060" xlink:to="loc_us-gaap_StatementTable_019fd051-c358-7bbd-a1e3-9ecb7e132963" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_019fd051-c358-7b01-85af-c6eb6c70324f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_019fd051-c358-7bbd-a1e3-9ecb7e132963" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_019fd051-c358-7b01-85af-c6eb6c70324f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_019fd051-c358-7b01-85af-c6eb6c70324f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_019fd051-c358-7b01-85af-c6eb6c70324f" xlink:to="loc_us-gaap_EquityComponentDomain_019fd051-c358-7b01-85af-c6eb6c70324f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_019fd051-c358-70c8-84f6-b63097610e31" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_019fd051-c358-7b01-85af-c6eb6c70324f" xlink:to="loc_us-gaap_EquityComponentDomain_019fd051-c358-70c8-84f6-b63097610e31" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_019fd051-c358-7391-9143-2a2eb0679d26" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019fd051-c358-70c8-84f6-b63097610e31" xlink:to="loc_us-gaap_CommonStockMember_019fd051-c358-7391-9143-2a2eb0679d26" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_019fd051-c358-7b9e-9e34-17c0e74101ff" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019fd051-c358-70c8-84f6-b63097610e31" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_019fd051-c358-7b9e-9e34-17c0e74101ff" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_019fd051-c358-7660-a111-652ee1a718f1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019fd051-c358-70c8-84f6-b63097610e31" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_019fd051-c358-7660-a111-652ee1a718f1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_019fd051-c358-7afa-a57a-d259e2890347" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019fd051-c358-70c8-84f6-b63097610e31" xlink:to="loc_us-gaap_RetainedEarningsMember_019fd051-c358-7afa-a57a-d259e2890347" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019fd051-c358-7e83-9cdf-d24977f6e9d0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019fd051-c358-7114-a99a-5e7fdd16c060" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019fd051-c358-7e83-9cdf-d24977f6e9d0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesOutstanding_019fd051-c358-7011-af20-93eaa432b076" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019fd051-c358-7e83-9cdf-d24977f6e9d0" xlink:to="loc_us-gaap_SharesOutstanding_019fd051-c358-7011-af20-93eaa432b076" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019fd051-c358-7a0f-9b21-141bb3f73ead" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019fd051-c358-7e83-9cdf-d24977f6e9d0" xlink:to="loc_us-gaap_StockholdersEquity_019fd051-c358-7a0f-9b21-141bb3f73ead" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_019fd051-c358-7182-9547-a6b6d0286f42" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019fd051-c358-7e83-9cdf-d24977f6e9d0" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_019fd051-c358-7182-9547-a6b6d0286f42" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation_019fd051-c358-72d0-9a29-d16fb0548e09" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019fd051-c358-7e83-9cdf-d24977f6e9d0" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation_019fd051-c358-72d0-9a29-d16fb0548e09" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_019fd051-c358-7d8f-ac87-72558ff2538e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019fd051-c358-7e83-9cdf-d24977f6e9d0" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_019fd051-c358-7d8f-ac87-72558ff2538e" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan_019fd051-c358-71f5-bcfb-c68887d7bc51" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019fd051-c358-7e83-9cdf-d24977f6e9d0" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan_019fd051-c358-71f5-bcfb-c68887d7bc51" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_019fd051-c358-7e98-86b4-9224ccff64c5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019fd051-c358-7e83-9cdf-d24977f6e9d0" xlink:to="loc_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_019fd051-c358-7e98-86b4-9224ccff64c5" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_019fd051-c358-7c37-9cb3-6e7a1107384e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019fd051-c358-7e83-9cdf-d24977f6e9d0" xlink:to="loc_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_019fd051-c358-7c37-9cb3-6e7a1107384e" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_019fd051-c358-75e8-a971-cf2619a8d44e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019fd051-c358-7e83-9cdf-d24977f6e9d0" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_019fd051-c358-75e8-a971-cf2619a8d44e" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent_019fd051-c358-7f03-91a3-918997f94773" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019fd051-c358-7e83-9cdf-d24977f6e9d0" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent_019fd051-c358-7f03-91a3-918997f94773" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_019fd051-c358-7d6e-a46a-ba549205c675" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019fd051-c358-7e83-9cdf-d24977f6e9d0" xlink:to="loc_us-gaap_NetIncomeLoss_019fd051-c358-7d6e-a46a-ba549205c675" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesOutstanding_019fd051-c358-70d1-96f5-08f68298675e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019fd051-c358-7ce3-9622-d45a128d6255" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockholdersEquity"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.penumbrainc.com/role/OrganizationandDescriptionofBusinessDetails" xlink:type="simple" xlink:href="pen-20260930.xsd#OrganizationandDescriptionofBusinessDetails"/>
  <link:definitionLink xlink:role="http://www.penumbrainc.com/role/OrganizationandDescriptionofBusinessDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionLineItems_019fd051-c358-72e4-81da-4f9a2c34f0a8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_019fd051-c358-7406-8f06-d58af10b20cd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_019fd051-c358-72e4-81da-4f9a2c34f0a8" xlink:to="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_019fd051-c358-7406-8f06-d58af10b20cd" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_019fd051-c358-7ca6-8743-1120f1ab80dc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_019fd051-c358-7406-8f06-d58af10b20cd" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_019fd051-c358-7ca6-8743-1120f1ab80dc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_019fd051-c358-7ca6-8743-1120f1ab80dc_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_019fd051-c358-7ca6-8743-1120f1ab80dc" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_019fd051-c358-7ca6-8743-1120f1ab80dc_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_019fd051-c358-7b79-98b2-26f7eb67b271" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_019fd051-c358-7ca6-8743-1120f1ab80dc" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_019fd051-c358-7b79-98b2-26f7eb67b271" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pen_MergerAgreementMember_019fd051-c358-79ed-b93b-954151886849" xlink:href="pen-20260930.xsd#pen_MergerAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_019fd051-c358-7b79-98b2-26f7eb67b271" xlink:to="loc_pen_MergerAgreementMember_019fd051-c358-79ed-b93b-954151886849" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_LegalEntityAxis_019fd051-c358-7722-97b1-f23911795c34" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_LegalEntityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_019fd051-c358-7406-8f06-d58af10b20cd" xlink:to="loc_dei_LegalEntityAxis_019fd051-c358-7722-97b1-f23911795c34" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityDomain_019fd051-c358-7722-97b1-f23911795c34_default" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_dei_LegalEntityAxis_019fd051-c358-7722-97b1-f23911795c34" xlink:to="loc_dei_EntityDomain_019fd051-c358-7722-97b1-f23911795c34_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityDomain_019fd051-c358-7488-b8e6-a429bf35064f" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_dei_LegalEntityAxis_019fd051-c358-7722-97b1-f23911795c34" xlink:to="loc_dei_EntityDomain_019fd051-c358-7488-b8e6-a429bf35064f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pen_BostonScientificCorporationMember_019fd051-c358-7c44-83cc-0ba2e266a3a8" xlink:href="pen-20260930.xsd#pen_BostonScientificCorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityDomain_019fd051-c358-7488-b8e6-a429bf35064f" xlink:to="loc_pen_BostonScientificCorporationMember_019fd051-c358-7c44-83cc-0ba2e266a3a8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionSharePrice_019fd051-c358-716a-bb93-15293e694deb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionSharePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_019fd051-c358-72e4-81da-4f9a2c34f0a8" xlink:to="loc_us-gaap_BusinessAcquisitionSharePrice_019fd051-c358-716a-bb93-15293e694deb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_pen_BusinessCombinationEnterpriseValue_019fd051-c358-7ff8-a9d6-946c00039e10" xlink:href="pen-20260930.xsd#pen_BusinessCombinationEnterpriseValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_019fd051-c358-72e4-81da-4f9a2c34f0a8" xlink:to="loc_pen_BusinessCombinationEnterpriseValue_019fd051-c358-7ff8-a9d6-946c00039e10" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pen_BusinessCombinationConsiderationTransferredEquityInterestsIssuedAndIssuableEntitySharesIssuedPerAcquireeShare_019fd051-c358-70ec-9efb-1ca734820efa" xlink:href="pen-20260930.xsd#pen_BusinessCombinationConsiderationTransferredEquityInterestsIssuedAndIssuableEntitySharesIssuedPerAcquireeShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_019fd051-c358-72e4-81da-4f9a2c34f0a8" xlink:to="loc_pen_BusinessCombinationConsiderationTransferredEquityInterestsIssuedAndIssuableEntitySharesIssuedPerAcquireeShare_019fd051-c358-70ec-9efb-1ca734820efa" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_pen_BusinessCombinationConsiderationTransferredEquityInterestsIssuedAndIssuableTradingDays_019fd051-c358-7548-a801-2562d86e6631" xlink:href="pen-20260930.xsd#pen_BusinessCombinationConsiderationTransferredEquityInterestsIssuedAndIssuableTradingDays"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_019fd051-c358-72e4-81da-4f9a2c34f0a8" xlink:to="loc_pen_BusinessCombinationConsiderationTransferredEquityInterestsIssuedAndIssuableTradingDays_019fd051-c358-7548-a801-2562d86e6631" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_pen_BusinessCombinationConsiderationCashPercent_019fd051-c358-7c92-87ac-e5e025be113e" xlink:href="pen-20260930.xsd#pen_BusinessCombinationConsiderationCashPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_019fd051-c358-72e4-81da-4f9a2c34f0a8" xlink:to="loc_pen_BusinessCombinationConsiderationCashPercent_019fd051-c358-7c92-87ac-e5e025be113e" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_pen_BusinessCombinationConsiderationEquityInterestPercent_019fd051-c358-7e93-912f-777e47a4ac0c" xlink:href="pen-20260930.xsd#pen_BusinessCombinationConsiderationEquityInterestPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_019fd051-c358-72e4-81da-4f9a2c34f0a8" xlink:to="loc_pen_BusinessCombinationConsiderationEquityInterestPercent_019fd051-c358-7e93-912f-777e47a4ac0c" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_pen_BusinessCombinationTerminationFee_019fd051-c358-710e-84b5-3e4f55ead446" xlink:href="pen-20260930.xsd#pen_BusinessCombinationTerminationFee"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_019fd051-c358-72e4-81da-4f9a2c34f0a8" xlink:to="loc_pen_BusinessCombinationTerminationFee_019fd051-c358-710e-84b5-3e4f55ead446" xlink:type="arc" order="6"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.penumbrainc.com/role/InvestmentsandFairValueofFinancialInstrumentsGainsandLossesofMarketableInvestmentsDetails" xlink:type="simple" xlink:href="pen-20260930.xsd#InvestmentsandFairValueofFinancialInstrumentsGainsandLossesofMarketableInvestmentsDetails"/>
  <link:definitionLink xlink:role="http://www.penumbrainc.com/role/InvestmentsandFairValueofFinancialInstrumentsGainsandLossesofMarketableInvestmentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019fd051-c358-7971-9f01-8c336459c8b0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_019fd051-c358-7d4c-b5cb-a623423a58f0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019fd051-c358-7971-9f01-8c336459c8b0" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_019fd051-c358-7d4c-b5cb-a623423a58f0" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_019fd051-c358-7d7d-943f-55d64cb7a50b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_019fd051-c358-7d4c-b5cb-a623423a58f0" xlink:to="loc_us-gaap_FinancialInstrumentAxis_019fd051-c358-7d7d-943f-55d64cb7a50b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-7d7d-943f-55d64cb7a50b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_019fd051-c358-7d7d-943f-55d64cb7a50b" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-7d7d-943f-55d64cb7a50b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-7f89-8fa4-b7535e6bc293" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_019fd051-c358-7d7d-943f-55d64cb7a50b" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-7f89-8fa4-b7535e6bc293" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember_019fd051-c358-77f4-b47b-704436edeb4d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-7f89-8fa4-b7535e6bc293" xlink:to="loc_us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember_019fd051-c358-77f4-b47b-704436edeb4d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CertificatesOfDepositMember_019fd051-c358-7469-88dc-3c5100c21a71" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CertificatesOfDepositMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-7f89-8fa4-b7535e6bc293" xlink:to="loc_us-gaap_CertificatesOfDepositMember_019fd051-c358-7469-88dc-3c5100c21a71" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_019fd051-c358-7519-8f4b-625dd2e4d504" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-7f89-8fa4-b7535e6bc293" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_019fd051-c358-7519-8f4b-625dd2e4d504" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_019fd051-c358-7402-8bb6-77aff930ff67" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-7f89-8fa4-b7535e6bc293" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_019fd051-c358-7402-8bb6-77aff930ff67" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_pen_NonMarketableInvestmentsMember_019fd051-c358-71ff-aa5c-daf4b3f24aee" xlink:href="pen-20260930.xsd#pen_NonMarketableInvestmentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-7f89-8fa4-b7535e6bc293" xlink:to="loc_pen_NonMarketableInvestmentsMember_019fd051-c358-71ff-aa5c-daf4b3f24aee" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_pen_MarketableAndNonMarketableInvestmentsMember_019fd051-c358-727d-9bb8-9655072a30f2" xlink:href="pen-20260930.xsd#pen_MarketableAndNonMarketableInvestmentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-7f89-8fa4-b7535e6bc293" xlink:to="loc_pen_MarketableAndNonMarketableInvestmentsMember_019fd051-c358-727d-9bb8-9655072a30f2" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_019fd051-c358-7b2e-b586-c74e4cc74b2a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019fd051-c358-7971-9f01-8c336459c8b0" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_019fd051-c358-7b2e-b586-c74e4cc74b2a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_019fd051-c358-73c3-8e8a-ce64c61a0c12" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019fd051-c358-7971-9f01-8c336459c8b0" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_019fd051-c358-73c3-8e8a-ce64c61a0c12" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_019fd051-c358-7f5e-b31a-ce44e58b1367" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019fd051-c358-7971-9f01-8c336459c8b0" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_019fd051-c358-7f5e-b31a-ce44e58b1367" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleAllowanceForCreditLoss_019fd051-c358-7b3b-9989-d2729cfc693b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleAllowanceForCreditLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019fd051-c358-7971-9f01-8c336459c8b0" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleAllowanceForCreditLoss_019fd051-c358-7b3b-9989-d2729cfc693b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_019fd051-c358-7741-b3f3-f8172b984b05" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019fd051-c358-7971-9f01-8c336459c8b0" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_019fd051-c358-7741-b3f3-f8172b984b05" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.penumbrainc.com/role/InvestmentsandFairValueofFinancialInstrumentsMarketableSecuritiesinanUnrealizedLossPositionDetails" xlink:type="simple" xlink:href="pen-20260930.xsd#InvestmentsandFairValueofFinancialInstrumentsMarketableSecuritiesinanUnrealizedLossPositionDetails"/>
  <link:definitionLink xlink:role="http://www.penumbrainc.com/role/InvestmentsandFairValueofFinancialInstrumentsMarketableSecuritiesinanUnrealizedLossPositionDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019fd051-c358-7f41-b391-799ae7d2b816" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_019fd051-c358-73e1-8ded-cd75655d5b44" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019fd051-c358-7f41-b391-799ae7d2b816" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_019fd051-c358-73e1-8ded-cd75655d5b44" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_019fd051-c358-75ca-9160-ccff52568d7a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_019fd051-c358-73e1-8ded-cd75655d5b44" xlink:to="loc_us-gaap_FinancialInstrumentAxis_019fd051-c358-75ca-9160-ccff52568d7a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-75ca-9160-ccff52568d7a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_019fd051-c358-75ca-9160-ccff52568d7a" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-75ca-9160-ccff52568d7a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-70a3-ab43-97f8dfcf75a0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_019fd051-c358-75ca-9160-ccff52568d7a" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-70a3-ab43-97f8dfcf75a0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember_019fd051-c358-79a1-8a11-93cfa2217853" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-70a3-ab43-97f8dfcf75a0" xlink:to="loc_us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember_019fd051-c358-79a1-8a11-93cfa2217853" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CertificatesOfDepositMember_019fd051-c358-7325-ad08-ea9dddd84480" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CertificatesOfDepositMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-70a3-ab43-97f8dfcf75a0" xlink:to="loc_us-gaap_CertificatesOfDepositMember_019fd051-c358-7325-ad08-ea9dddd84480" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_019fd051-c358-7f15-93a3-d8afb64be0c2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-70a3-ab43-97f8dfcf75a0" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_019fd051-c358-7f15-93a3-d8afb64be0c2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_019fd051-c358-7aed-8446-c9624283c8a3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-70a3-ab43-97f8dfcf75a0" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_019fd051-c358-7aed-8446-c9624283c8a3" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months_019fd051-c358-7263-8ab6-41a0c3c74606" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019fd051-c358-7f41-b391-799ae7d2b816" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months_019fd051-c358-7263-8ab6-41a0c3c74606" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_019fd051-c358-7d7d-bce3-843e7d01dc48" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019fd051-c358-7f41-b391-799ae7d2b816" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_019fd051-c358-7d7d-bce3-843e7d01dc48" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger_019fd051-c358-72fa-b612-0ae7ff8e7693" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019fd051-c358-7f41-b391-799ae7d2b816" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger_019fd051-c358-72fa-b612-0ae7ff8e7693" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_019fd051-c358-72cd-8ddd-8d8a7364b065" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019fd051-c358-7f41-b391-799ae7d2b816" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_019fd051-c358-72cd-8ddd-8d8a7364b065" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition_019fd051-c358-7c2c-9a95-18a1692e135c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019fd051-c358-7f41-b391-799ae7d2b816" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition_019fd051-c358-7c2c-9a95-18a1692e135c" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_019fd051-c358-72f7-acaf-305967ac830a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019fd051-c358-7f41-b391-799ae7d2b816" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_019fd051-c358-72f7-acaf-305967ac830a" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.penumbrainc.com/role/InvestmentsandFairValueofFinancialInstrumentsFinancialAssetsandLiabilitiesMeasuredatFairValueDetails" xlink:type="simple" xlink:href="pen-20260930.xsd#InvestmentsandFairValueofFinancialInstrumentsFinancialAssetsandLiabilitiesMeasuredatFairValueDetails"/>
  <link:definitionLink xlink:role="http://www.penumbrainc.com/role/InvestmentsandFairValueofFinancialInstrumentsFinancialAssetsandLiabilitiesMeasuredatFairValueDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019fd051-c358-77da-b304-bc3b91d89fe1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019fd051-c358-70dc-9e3d-25f80e75550d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019fd051-c358-77da-b304-bc3b91d89fe1" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019fd051-c358-70dc-9e3d-25f80e75550d" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019fd051-c358-70c7-8bcd-9ddfb8ad339f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019fd051-c358-70dc-9e3d-25f80e75550d" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019fd051-c358-70c7-8bcd-9ddfb8ad339f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019fd051-c358-70c7-8bcd-9ddfb8ad339f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019fd051-c358-70c7-8bcd-9ddfb8ad339f" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019fd051-c358-70c7-8bcd-9ddfb8ad339f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019fd051-c358-77f8-8add-4abb48cc0795" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019fd051-c358-70c7-8bcd-9ddfb8ad339f" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019fd051-c358-77f8-8add-4abb48cc0795" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_019fd051-c358-7358-b8b5-17730109444c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019fd051-c358-77f8-8add-4abb48cc0795" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_019fd051-c358-7358-b8b5-17730109444c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_019fd051-c358-7a78-81fc-cd921475378f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019fd051-c358-77f8-8add-4abb48cc0795" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_019fd051-c358-7a78-81fc-cd921475378f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel3Member_019fd051-c358-7f3c-a84e-f01c446c2525" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueInputsLevel3Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019fd051-c358-77f8-8add-4abb48cc0795" xlink:to="loc_us-gaap_FairValueInputsLevel3Member_019fd051-c358-7f3c-a84e-f01c446c2525" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAxis_019fd051-c358-7a07-82a9-4897ae8abf3d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CashAndCashEquivalentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019fd051-c358-70dc-9e3d-25f80e75550d" xlink:to="loc_us-gaap_CashAndCashEquivalentsAxis_019fd051-c358-7a07-82a9-4897ae8abf3d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019fd051-c358-7a07-82a9-4897ae8abf3d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_CashAndCashEquivalentsAxis_019fd051-c358-7a07-82a9-4897ae8abf3d" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019fd051-c358-7a07-82a9-4897ae8abf3d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019fd051-c358-7799-adea-42f898c26274" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_CashAndCashEquivalentsAxis_019fd051-c358-7a07-82a9-4897ae8abf3d" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019fd051-c358-7799-adea-42f898c26274" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommercialPaperMember_019fd051-c358-7dff-82ba-8767819ac664" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommercialPaperMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019fd051-c358-7799-adea-42f898c26274" xlink:to="loc_us-gaap_CommercialPaperMember_019fd051-c358-7dff-82ba-8767819ac664" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CertificatesOfDepositMember_019fd051-c358-78b4-92b9-cc10002a3f80" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CertificatesOfDepositMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019fd051-c358-7799-adea-42f898c26274" xlink:to="loc_us-gaap_CertificatesOfDepositMember_019fd051-c358-78b4-92b9-cc10002a3f80" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MoneyMarketFundsMember_019fd051-c358-7390-8a59-3263947ca5b6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MoneyMarketFundsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019fd051-c358-7799-adea-42f898c26274" xlink:to="loc_us-gaap_MoneyMarketFundsMember_019fd051-c358-7390-8a59-3263947ca5b6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_019fd051-c358-7243-9878-e66d412e0abe" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019fd051-c358-70dc-9e3d-25f80e75550d" xlink:to="loc_us-gaap_FinancialInstrumentAxis_019fd051-c358-7243-9878-e66d412e0abe" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-7243-9878-e66d412e0abe_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_019fd051-c358-7243-9878-e66d412e0abe" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-7243-9878-e66d412e0abe_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-70ee-85b2-c5abf66e1911" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_019fd051-c358-7243-9878-e66d412e0abe" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-70ee-85b2-c5abf66e1911" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember_019fd051-c358-7107-a05b-aa3acf555f6f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-70ee-85b2-c5abf66e1911" xlink:to="loc_us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember_019fd051-c358-7107-a05b-aa3acf555f6f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CertificatesOfDepositMember_019fd051-c358-703d-bd1e-52792605c962" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CertificatesOfDepositMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-70ee-85b2-c5abf66e1911" xlink:to="loc_us-gaap_CertificatesOfDepositMember_019fd051-c358-703d-bd1e-52792605c962" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_019fd051-c358-7652-ae0e-6698b6782ba9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-70ee-85b2-c5abf66e1911" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_019fd051-c358-7652-ae0e-6698b6782ba9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_019fd051-c358-7192-9263-de88e27d1ea7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019fd051-c358-70ee-85b2-c5abf66e1911" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_019fd051-c358-7192-9263-de88e27d1ea7" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentsFinancialAssetsBalanceSheetGroupingsAbstract_019fd051-c358-713d-9a07-e65fca016b6c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FinancialInstrumentsFinancialAssetsBalanceSheetGroupingsAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019fd051-c358-77da-b304-bc3b91d89fe1" xlink:to="loc_us-gaap_FinancialInstrumentsFinancialAssetsBalanceSheetGroupingsAbstract_019fd051-c358-713d-9a07-e65fca016b6c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_019fd051-c358-7d70-a113-b4bbb55d876c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsFinancialAssetsBalanceSheetGroupingsAbstract_019fd051-c358-713d-9a07-e65fca016b6c" xlink:to="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_019fd051-c358-7d70-a113-b4bbb55d876c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_019fd051-c358-7d2d-a86d-e11ad6f02d5d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsFinancialAssetsBalanceSheetGroupingsAbstract_019fd051-c358-713d-9a07-e65fca016b6c" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_019fd051-c358-7d2d-a86d-e11ad6f02d5d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_pen_NonMarketableSecuritiesFairValueDisclosures_019fd051-c358-7be5-b54b-6c12904558fc" xlink:href="pen-20260930.xsd#pen_NonMarketableSecuritiesFairValueDisclosures"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsFinancialAssetsBalanceSheetGroupingsAbstract_019fd051-c358-713d-9a07-e65fca016b6c" xlink:to="loc_pen_NonMarketableSecuritiesFairValueDisclosures_019fd051-c358-7be5-b54b-6c12904558fc" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_019fd051-c358-7f06-8741-cc91b4df438e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsFinancialAssetsBalanceSheetGroupingsAbstract_019fd051-c358-713d-9a07-e65fca016b6c" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_019fd051-c358-7f06-8741-cc91b4df438e" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.penumbrainc.com/role/IntangibleAssetsScheduleofAcquiredIntangibleAssetsDetails" xlink:type="simple" xlink:href="pen-20260930.xsd#IntangibleAssetsScheduleofAcquiredIntangibleAssetsDetails"/>
  <link:definitionLink xlink:role="http://www.penumbrainc.com/role/IntangibleAssetsScheduleofAcquiredIntangibleAssetsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019fd051-c402-7af4-bd57-86ccf201d34c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019fd051-c402-7051-8658-87da01a14ac8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019fd051-c402-7af4-bd57-86ccf201d34c" xlink:to="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019fd051-c402-7051-8658-87da01a14ac8" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_019fd051-c402-79f1-bd15-e3b5d14678d4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019fd051-c402-7051-8658-87da01a14ac8" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_019fd051-c402-79f1-bd15-e3b5d14678d4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_019fd051-c402-79f1-bd15-e3b5d14678d4_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_019fd051-c402-79f1-bd15-e3b5d14678d4" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_019fd051-c402-79f1-bd15-e3b5d14678d4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_019fd051-c402-75ed-96ab-817343feb47e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_019fd051-c402-79f1-bd15-e3b5d14678d4" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_019fd051-c402-75ed-96ab-817343feb47e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CustomerRelationshipsMember_019fd051-c402-731c-8f0e-83511d880f07" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CustomerRelationshipsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_019fd051-c402-75ed-96ab-817343feb47e" xlink:to="loc_us-gaap_CustomerRelationshipsMember_019fd051-c402-731c-8f0e-83511d880f07" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TradeSecretsMember_019fd051-c402-7abc-a263-05b54ce13a16" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TradeSecretsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_019fd051-c402-75ed-96ab-817343feb47e" xlink:to="loc_us-gaap_TradeSecretsMember_019fd051-c402-7abc-a263-05b54ce13a16" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsGross_019fd051-c402-7520-a85e-79dc3b50dcd1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019fd051-c402-7af4-bd57-86ccf201d34c" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsGross_019fd051-c402-7520-a85e-79dc3b50dcd1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_019fd051-c402-7547-9892-6d49e8b9f4c5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019fd051-c402-7af4-bd57-86ccf201d34c" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_019fd051-c402-7547-9892-6d49e8b9f4c5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsNet_019fd051-c402-72d9-982a-c0b340841dea" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019fd051-c402-7af4-bd57-86ccf201d34c" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsNet_019fd051-c402-72d9-982a-c0b340841dea" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.penumbrainc.com/role/IntangibleAssetsAdditionalInformationDetails" xlink:type="simple" xlink:href="pen-20260930.xsd#IntangibleAssetsAdditionalInformationDetails"/>
  <link:definitionLink xlink:role="http://www.penumbrainc.com/role/IntangibleAssetsAdditionalInformationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019fd051-c402-7224-ae9a-7e1c181dc0e7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019fd051-c402-786a-b8f5-732e9719fe1f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019fd051-c402-7224-ae9a-7e1c181dc0e7" xlink:to="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019fd051-c402-786a-b8f5-732e9719fe1f" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_019fd051-c402-772a-9c49-29699abef64d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019fd051-c402-786a-b8f5-732e9719fe1f" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_019fd051-c402-772a-9c49-29699abef64d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_019fd051-c402-772a-9c49-29699abef64d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_019fd051-c402-772a-9c49-29699abef64d" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_019fd051-c402-772a-9c49-29699abef64d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_019fd051-c402-7e65-bd78-24a5efdbe364" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_019fd051-c402-772a-9c49-29699abef64d" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_019fd051-c402-7e65-bd78-24a5efdbe364" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TradeSecretsMember_019fd051-c402-7d6d-bab3-efbf6a96d327" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TradeSecretsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_019fd051-c402-7e65-bd78-24a5efdbe364" xlink:to="loc_us-gaap_TradeSecretsMember_019fd051-c402-7d6d-bab3-efbf6a96d327" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsGross_019fd051-c402-79fc-ae0c-686030949eb9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019fd051-c402-7224-ae9a-7e1c181dc0e7" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsGross_019fd051-c402-79fc-ae0c-686030949eb9" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.penumbrainc.com/role/IntangibleAssetsAmortizationofFinitelivedIntangibleAssetsDetails" xlink:type="simple" xlink:href="pen-20260930.xsd#IntangibleAssetsAmortizationofFinitelivedIntangibleAssetsDetails"/>
  <link:definitionLink xlink:role="http://www.penumbrainc.com/role/IntangibleAssetsAmortizationofFinitelivedIntangibleAssetsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019fd051-c402-7bcd-b2a5-9edd2db617a5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019fd051-c402-7935-ac5a-ef9253b2dfe9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019fd051-c402-7bcd-b2a5-9edd2db617a5" xlink:to="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019fd051-c402-7935-ac5a-ef9253b2dfe9" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_019fd051-c402-77bf-90ad-81dfd02d9999" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementOfIncomeLocationBalanceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019fd051-c402-7935-ac5a-ef9253b2dfe9" xlink:to="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_019fd051-c402-77bf-90ad-81dfd02d9999" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfIntangibleAssets_019fd051-c402-7e13-983f-ef28d49aefda" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AmortizationOfIntangibleAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019fd051-c402-7bcd-b2a5-9edd2db617a5" xlink:to="loc_us-gaap_AmortizationOfIntangibleAssets_019fd051-c402-7e13-983f-ef28d49aefda" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.penumbrainc.com/role/IntangibleAssetsAmortizationofFinitelivedIntangibleAssetsDetails_1" xlink:type="simple" xlink:href="pen-20260930.xsd#IntangibleAssetsAmortizationofFinitelivedIntangibleAssetsDetails_1"/>
  <link:definitionLink xlink:role="http://www.penumbrainc.com/role/IntangibleAssetsAmortizationofFinitelivedIntangibleAssetsDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019fd051-c402-7bcd-b2a5-9edd2db617a5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019fd051-c402-7935-ac5a-ef9253b2dfe9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019fd051-c402-7bcd-b2a5-9edd2db617a5" xlink:to="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_019fd051-c402-7935-ac5a-ef9253b2dfe9" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfIntangibleAssets_019fd051-c402-7e13-983f-ef28d49aefda" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AmortizationOfIntangibleAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_019fd051-c402-7bcd-b2a5-9edd2db617a5" xlink:to="loc_us-gaap_AmortizationOfIntangibleAssets_019fd051-c402-7e13-983f-ef28d49aefda" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.penumbrainc.com/role/StockholdersEquityStockbasedCompensationExpenseDetails" xlink:type="simple" xlink:href="pen-20260930.xsd#StockholdersEquityStockbasedCompensationExpenseDetails"/>
  <link:definitionLink xlink:role="http://www.penumbrainc.com/role/StockholdersEquityStockbasedCompensationExpenseDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019fd051-c402-715e-87f3-f96399641507" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019fd051-c402-7f5c-a6d9-c8cf2f111f91" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019fd051-c402-715e-87f3-f96399641507" xlink:to="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019fd051-c402-7f5c-a6d9-c8cf2f111f91" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_019fd051-c402-725f-9c57-431d17a05161" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementOfIncomeLocationBalanceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019fd051-c402-7f5c-a6d9-c8cf2f111f91" xlink:to="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_019fd051-c402-725f-9c57-431d17a05161" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_019fd051-c402-7fb6-abec-37ef61801acb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019fd051-c402-715e-87f3-f96399641507" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_019fd051-c402-7fb6-abec-37ef61801acb" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.penumbrainc.com/role/StockholdersEquityStockbasedCompensationExpenseDetails_1" xlink:type="simple" xlink:href="pen-20260930.xsd#StockholdersEquityStockbasedCompensationExpenseDetails_1"/>
  <link:definitionLink xlink:role="http://www.penumbrainc.com/role/StockholdersEquityStockbasedCompensationExpenseDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019fd051-c402-715e-87f3-f96399641507" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019fd051-c402-7f5c-a6d9-c8cf2f111f91" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019fd051-c402-715e-87f3-f96399641507" xlink:to="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019fd051-c402-7f5c-a6d9-c8cf2f111f91" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_019fd051-c402-7fb6-abec-37ef61801acb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019fd051-c402-715e-87f3-f96399641507" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_019fd051-c402-7fb6-abec-37ef61801acb" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.penumbrainc.com/role/StockholdersEquityNarrativeDetails" xlink:type="simple" xlink:href="pen-20260930.xsd#StockholdersEquityNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.penumbrainc.com/role/StockholdersEquityNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019fd051-c402-7ebf-9b60-fe45faf57bfc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019fd051-c402-766d-beee-127e2a7bbde9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019fd051-c402-7ebf-9b60-fe45faf57bfc" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019fd051-c402-766d-beee-127e2a7bbde9" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019fd051-c402-7603-a390-756ff935be5c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019fd051-c402-766d-beee-127e2a7bbde9" xlink:to="loc_us-gaap_AwardTypeAxis_019fd051-c402-7603-a390-756ff935be5c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019fd051-c402-7603-a390-756ff935be5c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019fd051-c402-7603-a390-756ff935be5c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019fd051-c402-7603-a390-756ff935be5c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019fd051-c402-78de-89c6-20498809fb9c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019fd051-c402-7603-a390-756ff935be5c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019fd051-c402-78de-89c6-20498809fb9c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pen_NonPerformanceSharesMember_019fd051-c402-72e8-b7d5-399af5976c13" xlink:href="pen-20260930.xsd#pen_NonPerformanceSharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019fd051-c402-78de-89c6-20498809fb9c" xlink:to="loc_pen_NonPerformanceSharesMember_019fd051-c402-72e8-b7d5-399af5976c13" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PerformanceSharesMember_019fd051-c402-7ac7-a255-1147ce58af0d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PerformanceSharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019fd051-c402-78de-89c6-20498809fb9c" xlink:to="loc_us-gaap_PerformanceSharesMember_019fd051-c402-7ac7-a255-1147ce58af0d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized_019fd051-c402-7ce0-9542-fe72c0be07b4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019fd051-c402-7ebf-9b60-fe45faf57bfc" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized_019fd051-c402-7ce0-9542-fe72c0be07b4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_019fd051-c402-7b66-921c-e1107f0b74f7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019fd051-c402-7ebf-9b60-fe45faf57bfc" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_019fd051-c402-7b66-921c-e1107f0b74f7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount_019fd051-c402-7abe-be7f-ca70dead6ac8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019fd051-c402-7ebf-9b60-fe45faf57bfc" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount_019fd051-c402-7abe-be7f-ca70dead6ac8" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.penumbrainc.com/role/AccumulatedOtherComprehensiveIncomeDetails" xlink:type="simple" xlink:href="pen-20260930.xsd#AccumulatedOtherComprehensiveIncomeDetails"/>
  <link:definitionLink xlink:role="http://www.penumbrainc.com/role/AccumulatedOtherComprehensiveIncomeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossLineItems_019fd051-c402-73a9-8d0d-768ef8148c3a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossTable_019fd051-c402-7e71-8b45-e851506a4b9d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossLineItems_019fd051-c402-73a9-8d0d-768ef8148c3a" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossTable_019fd051-c402-7e71-8b45-e851506a4b9d" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_019fd051-c402-7904-a0c1-d07d680e37ae" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossTable_019fd051-c402-7e71-8b45-e851506a4b9d" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_019fd051-c402-7904-a0c1-d07d680e37ae" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_019fd051-c402-7904-a0c1-d07d680e37ae_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_019fd051-c402-7904-a0c1-d07d680e37ae" xlink:to="loc_us-gaap_EquityComponentDomain_019fd051-c402-7904-a0c1-d07d680e37ae_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_019fd051-c402-7d1e-9679-07676f596b7c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_019fd051-c402-7904-a0c1-d07d680e37ae" xlink:to="loc_us-gaap_EquityComponentDomain_019fd051-c402-7d1e-9679-07676f596b7c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_019fd051-c402-707b-80dd-dca976704a86" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019fd051-c402-7d1e-9679-07676f596b7c" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_019fd051-c402-707b-80dd-dca976704a86" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_pen_AOCIAccumulatedGainLossMarketableAndNonMarketableDebtSecuritiesAvailableForSaleParentMember_019fd051-c402-7e83-b3a7-2713a9b20837" xlink:href="pen-20260930.xsd#pen_AOCIAccumulatedGainLossMarketableAndNonMarketableDebtSecuritiesAvailableForSaleParentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_019fd051-c402-707b-80dd-dca976704a86" xlink:to="loc_pen_AOCIAccumulatedGainLossMarketableAndNonMarketableDebtSecuritiesAvailableForSaleParentMember_019fd051-c402-7e83-b3a7-2713a9b20837" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedNetUnrealizedInvestmentGainLossMember_019fd051-c402-76df-b1b1-8948856a5172" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccumulatedNetUnrealizedInvestmentGainLossMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pen_AOCIAccumulatedGainLossMarketableAndNonMarketableDebtSecuritiesAvailableForSaleParentMember_019fd051-c402-7e83-b3a7-2713a9b20837" xlink:to="loc_us-gaap_AccumulatedNetUnrealizedInvestmentGainLossMember_019fd051-c402-76df-b1b1-8948856a5172" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pen_AOCIAccumulatedGainLossNonMarketableDebtSecuritiesAvailableForSaleParentMember_019fd051-c402-7c57-ada0-28443ae9d3ad" xlink:href="pen-20260930.xsd#pen_AOCIAccumulatedGainLossNonMarketableDebtSecuritiesAvailableForSaleParentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pen_AOCIAccumulatedGainLossMarketableAndNonMarketableDebtSecuritiesAvailableForSaleParentMember_019fd051-c402-7e83-b3a7-2713a9b20837" xlink:to="loc_pen_AOCIAccumulatedGainLossNonMarketableDebtSecuritiesAvailableForSaleParentMember_019fd051-c402-7c57-ada0-28443ae9d3ad" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedTranslationAdjustmentMember_019fd051-c402-7d0f-82b0-7a14a9cf7c88" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccumulatedTranslationAdjustmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019fd051-c402-7d1e-9679-07676f596b7c" xlink:to="loc_us-gaap_AccumulatedTranslationAdjustmentMember_019fd051-c402-7d0f-82b0-7a14a9cf7c88" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AOCIAttributableToParentNetOfTaxRollForward_019fd051-c402-70aa-b1bd-15521d7767ae" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AOCIAttributableToParentNetOfTaxRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossLineItems_019fd051-c402-73a9-8d0d-768ef8148c3a" xlink:to="loc_us-gaap_AOCIAttributableToParentNetOfTaxRollForward_019fd051-c402-70aa-b1bd-15521d7767ae" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019fd051-c402-7210-a1ce-f6db7810879a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AOCIAttributableToParentNetOfTaxRollForward_019fd051-c402-70aa-b1bd-15521d7767ae" xlink:to="loc_us-gaap_StockholdersEquity_019fd051-c402-7210-a1ce-f6db7810879a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsTaxAbstract_019fd051-c402-7775-b0ba-028739130ae0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsTaxAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AOCIAttributableToParentNetOfTaxRollForward_019fd051-c402-70aa-b1bd-15521d7767ae" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsTaxAbstract_019fd051-c402-7775-b0ba-028739130ae0" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OciBeforeReclassificationsBeforeTaxAttributableToParent_019fd051-c402-74d4-8fb5-846ec6b9aca9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OciBeforeReclassificationsBeforeTaxAttributableToParent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsTaxAbstract_019fd051-c402-7775-b0ba-028739130ae0" xlink:to="loc_us-gaap_OciBeforeReclassificationsBeforeTaxAttributableToParent_019fd051-c402-74d4-8fb5-846ec6b9aca9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsTax_019fd051-c402-7055-9207-5815b4bf8147" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsTaxAbstract_019fd051-c402-7775-b0ba-028739130ae0" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsTax_019fd051-c402-7055-9207-5815b4bf8147" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OciBeforeReclassificationsNetOfTaxAttributableToParent_019fd051-c402-7c53-9fa9-685162ab7358" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OciBeforeReclassificationsNetOfTaxAttributableToParent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsTaxAbstract_019fd051-c402-7775-b0ba-028739130ae0" xlink:to="loc_us-gaap_OciBeforeReclassificationsNetOfTaxAttributableToParent_019fd051-c402-7c53-9fa9-685162ab7358" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent_019fd051-c402-726a-b6ef-b2a075a583ee" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AOCIAttributableToParentNetOfTaxRollForward_019fd051-c402-70aa-b1bd-15521d7767ae" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent_019fd051-c402-726a-b6ef-b2a075a583ee" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019fd051-c402-7ec2-ab49-607a70a1baee" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockholdersEquity"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.penumbrainc.com/role/RevenuesDisaggregationofRevenueDetails" xlink:type="simple" xlink:href="pen-20260930.xsd#RevenuesDisaggregationofRevenueDetails"/>
  <link:definitionLink xlink:role="http://www.penumbrainc.com/role/RevenuesDisaggregationofRevenueDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_019fd051-c402-7562-9db1-5bcc964819b1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_019fd051-c402-7eed-bba4-ab8b656e61bb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DisaggregationOfRevenueTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019fd051-c402-7562-9db1-5bcc964819b1" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_019fd051-c402-7eed-bba4-ab8b656e61bb" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019fd051-c402-770b-894d-4deccac8074f" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_019fd051-c402-7eed-bba4-ab8b656e61bb" xlink:to="loc_srt_ProductOrServiceAxis_019fd051-c402-770b-894d-4deccac8074f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019fd051-c402-770b-894d-4deccac8074f_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019fd051-c402-770b-894d-4deccac8074f" xlink:to="loc_srt_ProductsAndServicesDomain_019fd051-c402-770b-894d-4deccac8074f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019fd051-c402-7e36-8692-b2bbd200c6c6" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019fd051-c402-770b-894d-4deccac8074f" xlink:to="loc_srt_ProductsAndServicesDomain_019fd051-c402-7e36-8692-b2bbd200c6c6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pen_ThrombectomyMember_019fd051-c402-78b5-aba6-6888ee5e2030" xlink:href="pen-20260930.xsd#pen_ThrombectomyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019fd051-c402-7e36-8692-b2bbd200c6c6" xlink:to="loc_pen_ThrombectomyMember_019fd051-c402-78b5-aba6-6888ee5e2030" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_pen_EmbolizationAndAccessMember_019fd051-c402-7e06-a6a9-50561511ef01" xlink:href="pen-20260930.xsd#pen_EmbolizationAndAccessMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019fd051-c402-7e36-8692-b2bbd200c6c6" xlink:to="loc_pen_EmbolizationAndAccessMember_019fd051-c402-7e06-a6a9-50561511ef01" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementGeographicalAxis_019fd051-c402-7fc9-956e-a4490e9b3453" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_StatementGeographicalAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_019fd051-c402-7eed-bba4-ab8b656e61bb" xlink:to="loc_srt_StatementGeographicalAxis_019fd051-c402-7fc9-956e-a4490e9b3453" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_019fd051-c402-7fc9-956e-a4490e9b3453_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementGeographicalAxis_019fd051-c402-7fc9-956e-a4490e9b3453" xlink:to="loc_srt_SegmentGeographicalDomain_019fd051-c402-7fc9-956e-a4490e9b3453_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_019fd051-c402-7d0c-912b-091a9e72cb93" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementGeographicalAxis_019fd051-c402-7fc9-956e-a4490e9b3453" xlink:to="loc_srt_SegmentGeographicalDomain_019fd051-c402-7d0c-912b-091a9e72cb93" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_country_US_019fd051-c402-7b30-b3b2-0440e9ee7c35" xlink:href="https://xbrl.sec.gov/country/2026/country-2026.xsd#country_US"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_019fd051-c402-7d0c-912b-091a9e72cb93" xlink:to="loc_country_US_019fd051-c402-7b30-b3b2-0440e9ee7c35" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NonUsMember_019fd051-c402-7201-b48f-7826392c2ea3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NonUsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_019fd051-c402-7d0c-912b-091a9e72cb93" xlink:to="loc_us-gaap_NonUsMember_019fd051-c402-7201-b48f-7826392c2ea3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019fd051-c402-763e-bcc4-434c972b6742" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019fd051-c402-7562-9db1-5bcc964819b1" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019fd051-c402-763e-bcc4-434c972b6742" xlink:type="arc" order="0"/>
  </link:definitionLink>
</link:linkbase>
