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

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2026 Workiva-->
<!--r:019e40d0-8a31-7631-8e13-3b45528dbe68,g:5997007e-940b-44a0-8ed9-d99587778a7b-->
<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" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="https://xbrl.org/2023/arcrole/summation-item" xlink:type="simple" xlink:href="https://www.xbrl.org/2023/calculation-1.1.xsd#summation-item"/>
  <link:roleRef roleURI="http://www.ligand.com/role/CONDENSEDCONSOLIDATEDBALANCESHEETS" xlink:type="simple" xlink:href="lgnd-20260630.xsd#CONDENSEDCONSOLIDATEDBALANCESHEETS"/>
  <link:calculationLink xlink:role="http://www.ligand.com/role/CONDENSEDCONSOLIDATEDBALANCESHEETS" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesAndStockholdersEquity_019e40d0-8bc9-72a7-8d75-de46209d67fc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LiabilitiesAndStockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_019e40d0-8bc9-76b1-a4cb-5ac0ee2bf512" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_Liabilities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_019e40d0-8bc9-72a7-8d75-de46209d67fc" xlink:to="loc_us-gaap_Liabilities_019e40d0-8bc9-76b1-a4cb-5ac0ee2bf512" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019e40d0-8bc9-7c96-ac95-06378ad093ce" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockholdersEquity"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_019e40d0-8bc9-72a7-8d75-de46209d67fc" xlink:to="loc_us-gaap_StockholdersEquity_019e40d0-8bc9-7c96-ac95-06378ad093ce" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommitmentsAndContingencies_019e40d0-8bc9-74f0-98bd-4f5c56a94cfd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommitmentsAndContingencies"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_019e40d0-8bc9-72a7-8d75-de46209d67fc" xlink:to="loc_us-gaap_CommitmentsAndContingencies_019e40d0-8bc9-74f0-98bd-4f5c56a94cfd" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_019e40d0-8bc9-7088-9a5b-bd39d17fb123" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesCurrent_019e40d0-8bc9-7391-af5d-e11bcac75e4d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccruedLiabilitiesCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_019e40d0-8bc9-7088-9a5b-bd39d17fb123" xlink:to="loc_us-gaap_AccruedLiabilitiesCurrent_019e40d0-8bc9-7391-af5d-e11bcac75e4d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsPayableCurrent_019e40d0-8bc9-7295-a8d9-d05606f0bb2b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccountsPayableCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_019e40d0-8bc9-7088-9a5b-bd39d17fb123" xlink:to="loc_us-gaap_AccountsPayableCurrent_019e40d0-8bc9-7295-a8d9-d05606f0bb2b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_CurrentPortionOfLiabilityForContingentValueRights_019e40d0-8bc9-7165-9388-d5beb31c93e0" xlink:href="lgnd-20260630.xsd#lgnd_CurrentPortionOfLiabilityForContingentValueRights"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_019e40d0-8bc9-7088-9a5b-bd39d17fb123" xlink:to="loc_lgnd_CurrentPortionOfLiabilityForContingentValueRights_019e40d0-8bc9-7165-9388-d5beb31c93e0" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesCurrent_019e40d0-8bc9-70a9-808e-53bb898a32bd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherLiabilitiesCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_019e40d0-8bc9-7088-9a5b-bd39d17fb123" xlink:to="loc_us-gaap_OtherLiabilitiesCurrent_019e40d0-8bc9-70a9-808e-53bb898a32bd" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TaxesPayableCurrent_019e40d0-8bc9-78bc-a8c3-3d4587d2bea9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TaxesPayableCurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_019e40d0-8bc9-7088-9a5b-bd39d17fb123" xlink:to="loc_us-gaap_TaxesPayableCurrent_019e40d0-8bc9-78bc-a8c3-3d4587d2bea9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityCurrent_019e40d0-8bc9-7680-b6fc-d5cbdd1816ab" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingLeaseLiabilityCurrent"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_019e40d0-8bc9-7088-9a5b-bd39d17fb123" xlink:to="loc_us-gaap_OperatingLeaseLiabilityCurrent_019e40d0-8bc9-7680-b6fc-d5cbdd1816ab" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_019e40d0-8bc9-76ff-a26a-a3ff967b1526" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetsCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsCurrent_019e40d0-8bc9-746b-b233-bf7d59461e61" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherAssetsCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_019e40d0-8bc9-76ff-a26a-a3ff967b1526" xlink:to="loc_us-gaap_OtherAssetsCurrent_019e40d0-8bc9-746b-b233-bf7d59461e61" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_019e40d0-8bc9-77ab-973e-14ad1438c9f2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_019e40d0-8bc9-76ff-a26a-a3ff967b1526" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_019e40d0-8bc9-77ab-973e-14ad1438c9f2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermInvestments_019e40d0-8bc9-7c6e-94e9-758e24e9629f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShortTermInvestments"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_019e40d0-8bc9-76ff-a26a-a3ff967b1526" xlink:to="loc_us-gaap_ShortTermInvestments_019e40d0-8bc9-7c6e-94e9-758e24e9629f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxesReceivable_019e40d0-8bc9-734e-874b-e4a5e04dd63f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncomeTaxesReceivable"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_019e40d0-8bc9-76ff-a26a-a3ff967b1526" xlink:to="loc_us-gaap_IncomeTaxesReceivable_019e40d0-8bc9-734e-874b-e4a5e04dd63f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableNetCurrent_019e40d0-8bc9-7ac1-83e9-e4e23cb037d7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccountsReceivableNetCurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_019e40d0-8bc9-76ff-a26a-a3ff967b1526" xlink:to="loc_us-gaap_AccountsReceivableNetCurrent_019e40d0-8bc9-7ac1-83e9-e4e23cb037d7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryNet_019e40d0-8bc9-71f4-83b6-72ce2673106c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InventoryNet"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_019e40d0-8bc9-76ff-a26a-a3ff967b1526" xlink:to="loc_us-gaap_InventoryNet_019e40d0-8bc9-71f4-83b6-72ce2673106c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FinancialRoyaltyAssetsCurrent_019e40d0-8bc9-7b96-b45e-e04519142c17" xlink:href="lgnd-20260630.xsd#lgnd_FinancialRoyaltyAssetsCurrent"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_019e40d0-8bc9-76ff-a26a-a3ff967b1526" xlink:to="loc_lgnd_FinancialRoyaltyAssetsCurrent_019e40d0-8bc9-7b96-b45e-e04519142c17" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Assets_019e40d0-8bc9-7cbd-965e-3dcfcbdeb485" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_Assets"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FinancialRoyaltyAssetsNonCurrent_019e40d0-8bc9-7dd4-8833-d348d642c74a" xlink:href="lgnd-20260630.xsd#lgnd_FinancialRoyaltyAssetsNonCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019e40d0-8bc9-7cbd-965e-3dcfcbdeb485" xlink:to="loc_lgnd_FinancialRoyaltyAssetsNonCurrent_019e40d0-8bc9-7dd4-8833-d348d642c74a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredIncomeTaxAssetsNet_019e40d0-8bc9-7ea5-b59c-525fb9ac59d7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DeferredIncomeTaxAssetsNet"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019e40d0-8bc9-7cbd-965e-3dcfcbdeb485" xlink:to="loc_us-gaap_DeferredIncomeTaxAssetsNet_019e40d0-8bc9-7ea5-b59c-525fb9ac59d7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_019e40d0-8bc9-7c51-b16d-c1d3a7140c93" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetsCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019e40d0-8bc9-7cbd-965e-3dcfcbdeb485" xlink:to="loc_us-gaap_AssetsCurrent_019e40d0-8bc9-7c51-b16d-c1d3a7140c93" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsNoncurrent_019e40d0-8bc9-773a-974c-1d8961a664c5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherAssetsNoncurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019e40d0-8bc9-7cbd-965e-3dcfcbdeb485" xlink:to="loc_us-gaap_OtherAssetsNoncurrent_019e40d0-8bc9-773a-974c-1d8961a664c5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IntangibleAssetsNetExcludingGoodwill_019e40d0-8bc9-7875-b61f-1ff19c9c58f6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IntangibleAssetsNetExcludingGoodwill"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019e40d0-8bc9-7cbd-965e-3dcfcbdeb485" xlink:to="loc_us-gaap_IntangibleAssetsNetExcludingGoodwill_019e40d0-8bc9-7875-b61f-1ff19c9c58f6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestments_019e40d0-8bc9-745d-adfc-ca195c1e8a46" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityMethodInvestments"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019e40d0-8bc9-7cbd-965e-3dcfcbdeb485" xlink:to="loc_us-gaap_EquityMethodInvestments_019e40d0-8bc9-745d-adfc-ca195c1e8a46" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Goodwill_019e40d0-8bc9-770c-8cab-bb42831a6980" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_Goodwill"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019e40d0-8bc9-7cbd-965e-3dcfcbdeb485" xlink:to="loc_us-gaap_Goodwill_019e40d0-8bc9-770c-8cab-bb42831a6980" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherInvestments_019e40d0-8bc9-7875-aae0-595456eabc54" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherInvestments"/>
    <link:calculationArc order="8" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019e40d0-8bc9-7cbd-965e-3dcfcbdeb485" xlink:to="loc_us-gaap_OtherInvestments_019e40d0-8bc9-7875-aae0-595456eabc54" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeAssetsNoncurrent_019e40d0-8bc9-7666-af83-65faebd87473" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DerivativeAssetsNoncurrent"/>
    <link:calculationArc order="9" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019e40d0-8bc9-7cbd-965e-3dcfcbdeb485" xlink:to="loc_us-gaap_DerivativeAssetsNoncurrent_019e40d0-8bc9-7666-af83-65faebd87473" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019e40d0-8bc9-7b8c-9669-411b240c0538" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsAccumulatedDeficit_019e40d0-8bc9-7299-9b87-21402af149d4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RetainedEarningsAccumulatedDeficit"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_019e40d0-8bc9-7b8c-9669-411b240c0538" xlink:to="loc_us-gaap_RetainedEarningsAccumulatedDeficit_019e40d0-8bc9-7299-9b87-21402af149d4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockValue_019e40d0-8bc9-7bd7-9c7c-b8c1641ebf81" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockValue"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_019e40d0-8bc9-7b8c-9669-411b240c0538" xlink:to="loc_us-gaap_CommonStockValue_019e40d0-8bc9-7bd7-9c7c-b8c1641ebf81" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapital_019e40d0-8bc9-7509-95c8-36aa8d69eea2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AdditionalPaidInCapital"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_019e40d0-8bc9-7b8c-9669-411b240c0538" xlink:to="loc_us-gaap_AdditionalPaidInCapital_019e40d0-8bc9-7509-95c8-36aa8d69eea2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_019e40d0-8bc9-75b2-8bc6-1fe0c65b383b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_019e40d0-8bc9-7b8c-9669-411b240c0538" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_019e40d0-8bc9-75b2-8bc6-1fe0c65b383b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockValue_019e40d0-8bc9-7b0b-991a-3e97d2956d62" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PreferredStockValue"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_019e40d0-8bc9-7b8c-9669-411b240c0538" xlink:to="loc_us-gaap_PreferredStockValue_019e40d0-8bc9-7b0b-991a-3e97d2956d62" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_019e40d0-8bc9-7b64-9297-61296927c4b2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_Liabilities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_019e40d0-8bc9-7c87-a40e-94930470fd27" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_019e40d0-8bc9-7b64-9297-61296927c4b2" xlink:to="loc_us-gaap_LiabilitiesCurrent_019e40d0-8bc9-7c87-a40e-94930470fd27" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeniorLongTermNotes_019e40d0-8bc9-7b56-805e-d36b8e1475d5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SeniorLongTermNotes"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_019e40d0-8bc9-7b64-9297-61296927c4b2" xlink:to="loc_us-gaap_SeniorLongTermNotes_019e40d0-8bc9-7b56-805e-d36b8e1475d5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_019e40d0-8bc9-7517-bb55-867f5059ba8f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_019e40d0-8bc9-7b64-9297-61296927c4b2" xlink:to="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_019e40d0-8bc9-7517-bb55-867f5059ba8f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_LiabilityForContingentValueRights_019e40d0-8bc9-73d4-8ebe-1de42da2eb9d" xlink:href="lgnd-20260630.xsd#lgnd_LiabilityForContingentValueRights"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_019e40d0-8bc9-7b64-9297-61296927c4b2" xlink:to="loc_lgnd_LiabilityForContingentValueRights_019e40d0-8bc9-73d4-8ebe-1de42da2eb9d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesNoncurrent_019e40d0-8bc9-76ed-b1bb-18a6944d7839" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherLiabilitiesNoncurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_019e40d0-8bc9-7b64-9297-61296927c4b2" xlink:to="loc_us-gaap_OtherLiabilitiesNoncurrent_019e40d0-8bc9-76ed-b1bb-18a6944d7839" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredIncomeTaxLiabilitiesNet_019e40d0-8bc9-759d-966d-4984d9be72cc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DeferredIncomeTaxLiabilitiesNet"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_019e40d0-8bc9-7b64-9297-61296927c4b2" xlink:to="loc_us-gaap_DeferredIncomeTaxLiabilitiesNet_019e40d0-8bc9-759d-966d-4984d9be72cc" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ligand.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFOPERATIONS" xlink:type="simple" xlink:href="lgnd-20260630.xsd#CONDENSEDCONSOLIDATEDSTATEMENTSOFOPERATIONS"/>
  <link:calculationLink xlink:role="http://www.ligand.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFOPERATIONS" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_019e40d0-8bc9-77e1-93c9-499400793d7c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_019e40d0-8bc9-7190-b0d5-95e84467686d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_019e40d0-8bc9-77e1-93c9-499400793d7c" xlink:to="loc_us-gaap_OperatingIncomeLoss_019e40d0-8bc9-7190-b0d5-95e84467686d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NonoperatingIncomeExpense_019e40d0-8bc9-7df7-9464-2b97079bb4e3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NonoperatingIncomeExpense"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_019e40d0-8bc9-77e1-93c9-499400793d7c" xlink:to="loc_us-gaap_NonoperatingIncomeExpense_019e40d0-8bc9-7df7-9464-2b97079bb4e3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NonoperatingIncomeExpense_019e40d0-8bc9-79be-a22d-9c6218d8aa97" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NonoperatingIncomeExpense"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainLossOnInvestments_019e40d0-8bc9-7772-822c-c08ce550ecf5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GainLossOnInvestments"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NonoperatingIncomeExpense_019e40d0-8bc9-79be-a22d-9c6218d8aa97" xlink:to="loc_us-gaap_GainLossOnInvestments_019e40d0-8bc9-7772-822c-c08ce550ecf5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_GainLossFromChangeInFairValueOfEquityMethodInvestmentsAndOtherInvestments_019e40d0-8bc9-74f9-8332-54bdbe813f08" xlink:href="lgnd-20260630.xsd#lgnd_GainLossFromChangeInFairValueOfEquityMethodInvestmentsAndOtherInvestments"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NonoperatingIncomeExpense_019e40d0-8bc9-79be-a22d-9c6218d8aa97" xlink:to="loc_lgnd_GainLossFromChangeInFairValueOfEquityMethodInvestmentsAndOtherInvestments_019e40d0-8bc9-74f9-8332-54bdbe813f08" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentIncomeInterest_019e40d0-8bc9-7054-b601-12c21875dd29" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InvestmentIncomeInterest"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NonoperatingIncomeExpense_019e40d0-8bc9-79be-a22d-9c6218d8aa97" xlink:to="loc_us-gaap_InvestmentIncomeInterest_019e40d0-8bc9-7054-b601-12c21875dd29" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseNonoperating_019e40d0-8bc9-7d7c-9a36-6913f0373064" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InterestExpenseNonoperating"/>
    <link:calculationArc order="4" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NonoperatingIncomeExpense_019e40d0-8bc9-79be-a22d-9c6218d8aa97" xlink:to="loc_us-gaap_InterestExpenseNonoperating_019e40d0-8bc9-7d7c-9a36-6913f0373064" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpense_019e40d0-8bc9-7855-b9f8-b66a5bbcef6c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherNonoperatingIncomeExpense"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NonoperatingIncomeExpense_019e40d0-8bc9-79be-a22d-9c6218d8aa97" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpense_019e40d0-8bc9-7855-b9f8-b66a5bbcef6c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_019e40d0-8bc9-7fb4-87ce-9370ee77d6f4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_019e40d0-8bc9-7d16-8bd9-8bd33b743396" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_019e40d0-8bc9-7fb4-87ce-9370ee77d6f4" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_019e40d0-8bc9-7d16-8bd9-8bd33b743396" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_019e40d0-8bc9-7779-ac28-ddc4eb8c6bdb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_019e40d0-8bc9-7fb4-87ce-9370ee77d6f4" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_019e40d0-8bc9-7779-ac28-ddc4eb8c6bdb" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_019e40d0-8bc9-7027-b078-e0115ccf1006" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019e40d0-8bc9-7138-943f-677fd2f2e69d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_019e40d0-8bc9-7027-b078-e0115ccf1006" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019e40d0-8bc9-7138-943f-677fd2f2e69d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingCostsAndExpenses_019e40d0-8bc9-76be-805e-f164069f59c8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingCostsAndExpenses"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_019e40d0-8bc9-7027-b078-e0115ccf1006" xlink:to="loc_us-gaap_OperatingCostsAndExpenses_019e40d0-8bc9-76be-805e-f164069f59c8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingCostsAndExpenses_019e40d0-8bc9-7428-b9ca-6e228b571d11" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingCostsAndExpenses"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostDirectMaterial_019e40d0-8bc9-78e5-85d8-980bd8e9df94" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CostDirectMaterial"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingCostsAndExpenses_019e40d0-8bc9-7428-b9ca-6e228b571d11" xlink:to="loc_us-gaap_CostDirectMaterial_019e40d0-8bc9-78e5-85d8-980bd8e9df94" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSoldAmortization_019e40d0-8bc9-742e-9d0e-29f81af46745" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CostOfGoodsAndServicesSoldAmortization"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingCostsAndExpenses_019e40d0-8bc9-7428-b9ca-6e228b571d11" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSoldAmortization_019e40d0-8bc9-742e-9d0e-29f81af46745" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_019e40d0-8bc9-7153-9bc0-0d71f9c31661" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingCostsAndExpenses_019e40d0-8bc9-7428-b9ca-6e228b571d11" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_019e40d0-8bc9-7153-9bc0-0d71f9c31661" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpense_019e40d0-8bc9-7709-bd38-74be0b775b8c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GeneralAndAdministrativeExpense"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingCostsAndExpenses_019e40d0-8bc9-7428-b9ca-6e228b571d11" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpense_019e40d0-8bc9-7709-bd38-74be0b775b8c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeGainLossOnDerivativeNet_019e40d0-8bc9-70bd-9be3-56fa1a5d01d9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DerivativeGainLossOnDerivativeNet"/>
    <link:calculationArc order="5" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingCostsAndExpenses_019e40d0-8bc9-7428-b9ca-6e228b571d11" xlink:to="loc_us-gaap_DerivativeGainLossOnDerivativeNet_019e40d0-8bc9-70bd-9be3-56fa1a5d01d9" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ligand.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFCOMPREHENSIVEINCOMELOSS" xlink:type="simple" xlink:href="lgnd-20260630.xsd#CONDENSEDCONSOLIDATEDSTATEMENTSOFCOMPREHENSIVEINCOMELOSS"/>
  <link:calculationLink xlink:role="http://www.ligand.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFCOMPREHENSIVEINCOMELOSS" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComprehensiveIncomeNetOfTax_019e40d0-8bc9-7996-b8f0-91abcafaba53" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ComprehensiveIncomeNetOfTax"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_019e40d0-8bc9-7700-a7fc-389d750b06db" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_019e40d0-8bc9-7996-b8f0-91abcafaba53" xlink:to="loc_us-gaap_NetIncomeLoss_019e40d0-8bc9-7700-a7fc-389d750b06db" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_019e40d0-8bc9-7642-ba58-27e6bad255e0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_019e40d0-8bc9-7996-b8f0-91abcafaba53" xlink:to="loc_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_019e40d0-8bc9-7642-ba58-27e6bad255e0" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationAdjustmentNetOfTaxPortionAttributableToParent_019e40d0-8bc9-7479-8ae0-9bc3ca2c4bfd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationAdjustmentNetOfTaxPortionAttributableToParent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_019e40d0-8bc9-7996-b8f0-91abcafaba53" xlink:to="loc_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationAdjustmentNetOfTaxPortionAttributableToParent_019e40d0-8bc9-7479-8ae0-9bc3ca2c4bfd" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ligand.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFCASHFLOWS" xlink:type="simple" xlink:href="lgnd-20260630.xsd#CONDENSEDCONSOLIDATEDSTATEMENTSOFCASHFLOWS"/>
  <link:calculationLink xlink:role="http://www.ligand.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFCASHFLOWS" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_019e40d0-8bc9-74cd-98aa-b777182b1170" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:to="loc_us-gaap_NetIncomeLoss_019e40d0-8bc9-74cd-98aa-b777182b1170" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_NonCashChangeInEstimatedFairValueOfContingentValueRights_019e40d0-8bc9-7af1-bcdf-408be1ecb214" xlink:href="lgnd-20260630.xsd#lgnd_NonCashChangeInEstimatedFairValueOfContingentValueRights"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:to="loc_lgnd_NonCashChangeInEstimatedFairValueOfContingentValueRights_019e40d0-8bc9-7af1-bcdf-408be1ecb214" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DepreciationDepletionAndAmortization_019e40d0-8bc9-7639-a81c-70395bfebadc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DepreciationDepletionAndAmortization"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:to="loc_us-gaap_DepreciationDepletionAndAmortization_019e40d0-8bc9-7639-a81c-70395bfebadc" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments_019e40d0-8bc9-7229-8033-5cb6d5bf6041" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments"/>
    <link:calculationArc order="4" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:to="loc_us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments_019e40d0-8bc9-7229-8033-5cb6d5bf6041" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfFinancingCostsAndDiscounts_019e40d0-8bc9-7e13-93aa-cd8636dee7e2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AmortizationOfFinancingCostsAndDiscounts"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:to="loc_us-gaap_AmortizationOfFinancingCostsAndDiscounts_019e40d0-8bc9-7e13-93aa-cd8636dee7e2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_NonCashIncomeFromFinancialRoyaltyAssets_019e40d0-8bc9-738d-a32f-e1fa4b912d0c" xlink:href="lgnd-20260630.xsd#lgnd_NonCashIncomeFromFinancialRoyaltyAssets"/>
    <link:calculationArc order="6" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:to="loc_lgnd_NonCashIncomeFromFinancialRoyaltyAssets_019e40d0-8bc9-738d-a32f-e1fa4b912d0c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_CurrentAndExpectedCreditLossAdjustment_019e40d0-8bc9-7498-bdaa-5b4b51a22a1e" xlink:href="lgnd-20260630.xsd#lgnd_CurrentAndExpectedCreditLossAdjustment"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:to="loc_lgnd_CurrentAndExpectedCreditLossAdjustment_019e40d0-8bc9-7498-bdaa-5b4b51a22a1e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnrealizedGainLossOnDerivatives_019e40d0-8bc9-79f9-85af-217cb112f5df" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_UnrealizedGainLossOnDerivatives"/>
    <link:calculationArc order="8" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:to="loc_us-gaap_UnrealizedGainLossOnDerivatives_019e40d0-8bc9-79f9-85af-217cb112f5df" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquitySecuritiesFvNiUnrealizedGainLoss_019e40d0-8bc9-7de8-acc0-1318af3c671e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquitySecuritiesFvNiUnrealizedGainLoss"/>
    <link:calculationArc order="9" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:to="loc_us-gaap_EquitySecuritiesFvNiUnrealizedGainLoss_019e40d0-8bc9-7de8-acc0-1318af3c671e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensation_019e40d0-8bc9-754f-abb9-9c1d076760c6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensation"/>
    <link:calculationArc order="10" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:to="loc_us-gaap_ShareBasedCompensation_019e40d0-8bc9-754f-abb9-9c1d076760c6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInDeferredIncomeTaxes_019e40d0-8bc9-79b3-93da-4e6a10bf1d98" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncreaseDecreaseInDeferredIncomeTaxes"/>
    <link:calculationArc order="11" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:to="loc_us-gaap_IncreaseDecreaseInDeferredIncomeTaxes_019e40d0-8bc9-79b3-93da-4e6a10bf1d98" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_GainLossOnShortTermInvestments_019e40d0-8bc9-777b-ad72-83a38698c57a" xlink:href="lgnd-20260630.xsd#lgnd_GainLossOnShortTermInvestments"/>
    <link:calculationArc order="12" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:to="loc_lgnd_GainLossOnShortTermInvestments_019e40d0-8bc9-777b-ad72-83a38698c57a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FinanceLeaseAndOperatingLeaseRightOfUseAssetAmortization_019e40d0-8bc9-7049-bdb5-e427c30e40b7" xlink:href="lgnd-20260630.xsd#lgnd_FinanceLeaseAndOperatingLeaseRightOfUseAssetAmortization"/>
    <link:calculationArc order="13" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:to="loc_lgnd_FinanceLeaseAndOperatingLeaseRightOfUseAssetAmortization_019e40d0-8bc9-7049-bdb5-e427c30e40b7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherOperatingActivitiesCashFlowStatement_019e40d0-8bc9-7c46-ada4-56f36f191dbf" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherOperatingActivitiesCashFlowStatement"/>
    <link:calculationArc order="14" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:to="loc_us-gaap_OtherOperatingActivitiesCashFlowStatement_019e40d0-8bc9-7c46-ada4-56f36f191dbf" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccountsReceivable_019e40d0-8bc9-7cf4-8efc-fd858e1d682f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncreaseDecreaseInAccountsReceivable"/>
    <link:calculationArc order="15" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:to="loc_us-gaap_IncreaseDecreaseInAccountsReceivable_019e40d0-8bc9-7cf4-8efc-fd858e1d682f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInInventories_019e40d0-8bc9-7195-9434-5147cf2d07dd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncreaseDecreaseInInventories"/>
    <link:calculationArc order="16" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:to="loc_us-gaap_IncreaseDecreaseInInventories_019e40d0-8bc9-7195-9434-5147cf2d07dd" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccountsPayableAndAccruedLiabilities_019e40d0-8bc9-7e52-bd5a-050cdf5735ff" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncreaseDecreaseInAccountsPayableAndAccruedLiabilities"/>
    <link:calculationArc order="17" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:to="loc_us-gaap_IncreaseDecreaseInAccountsPayableAndAccruedLiabilities_019e40d0-8bc9-7e52-bd5a-050cdf5735ff" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInIncomeTaxesReceivable_019e40d0-8bc9-7820-852b-d17363f6470d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncreaseDecreaseInIncomeTaxesReceivable"/>
    <link:calculationArc order="18" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:to="loc_us-gaap_IncreaseDecreaseInIncomeTaxesReceivable_019e40d0-8bc9-7820-852b-d17363f6470d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInContractWithCustomerLiability_019e40d0-8bc9-73ae-8727-7c261f758bfb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncreaseDecreaseInContractWithCustomerLiability"/>
    <link:calculationArc order="19" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:to="loc_us-gaap_IncreaseDecreaseInContractWithCustomerLiability_019e40d0-8bc9-73ae-8727-7c261f758bfb" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInOtherOperatingCapitalNet_019e40d0-8bc9-76a1-8185-f4580fb6486b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncreaseDecreaseInOtherOperatingCapitalNet"/>
    <link:calculationArc order="20" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-7a33-b7e7-529e8c945811" xlink:to="loc_us-gaap_IncreaseDecreaseInOtherOperatingCapitalNet_019e40d0-8bc9-76a1-8185-f4580fb6486b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019f8a34-0646-7487-ac0d-91fb498bf133" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromConvertibleDebt_019f8a34-0646-74ff-96d9-2e2f009dc60e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ProceedsFromConvertibleDebt"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019f8a34-0646-7487-ac0d-91fb498bf133" xlink:to="loc_us-gaap_ProceedsFromConvertibleDebt_019f8a34-0646-74ff-96d9-2e2f009dc60e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsOfDebtIssuanceCosts_019f8a34-0646-7eac-a07c-e4b0925afa23" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsOfDebtIssuanceCosts"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019f8a34-0646-7487-ac0d-91fb498bf133" xlink:to="loc_us-gaap_PaymentsOfDebtIssuanceCosts_019f8a34-0646-7eac-a07c-e4b0925afa23" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForDerivativeInstrumentFinancingActivities_019f8a34-0646-7c79-b3d1-35c1dfebea2b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsForDerivativeInstrumentFinancingActivities"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019f8a34-0646-7487-ac0d-91fb498bf133" xlink:to="loc_us-gaap_PaymentsForDerivativeInstrumentFinancingActivities_019f8a34-0646-7c79-b3d1-35c1dfebea2b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfWarrants_019f8a34-0646-7265-b085-5d61c0ff53e7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ProceedsFromIssuanceOfWarrants"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019f8a34-0646-7487-ac0d-91fb498bf133" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfWarrants_019f8a34-0646-7265-b085-5d61c0ff53e7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForRepurchaseOfCommonStock_019f8a34-0646-756c-91a4-fd0acc0081ed" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsForRepurchaseOfCommonStock"/>
    <link:calculationArc order="5" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019f8a34-0646-7487-ac0d-91fb498bf133" xlink:to="loc_us-gaap_PaymentsForRepurchaseOfCommonStock_019f8a34-0646-756c-91a4-fd0acc0081ed" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeasePrincipalPayments_019f8a34-0646-757e-9437-194f448ac655" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FinanceLeasePrincipalPayments"/>
    <link:calculationArc order="6" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019f8a34-0646-7487-ac0d-91fb498bf133" xlink:to="loc_us-gaap_FinanceLeasePrincipalPayments_019f8a34-0646-757e-9437-194f448ac655" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromStockOptionsExercised_019f8a34-0646-78aa-9b13-a7862eeb3723" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ProceedsFromStockOptionsExercised"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019f8a34-0646-7487-ac0d-91fb498bf133" xlink:to="loc_us-gaap_ProceedsFromStockOptionsExercised_019f8a34-0646-78aa-9b13-a7862eeb3723" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_019f8a34-0646-7c00-9844-866370b0e170" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation"/>
    <link:calculationArc order="8" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019f8a34-0646-7487-ac0d-91fb498bf133" xlink:to="loc_us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_019f8a34-0646-7c00-9844-866370b0e170" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ProceedsFromInvestorsFinancingActivities_019f8a34-0646-79e1-b0e2-b0ef42fa0bcc" xlink:href="lgnd-20260630.xsd#lgnd_ProceedsFromInvestorsFinancingActivities"/>
    <link:calculationArc order="9" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019f8a34-0646-7487-ac0d-91fb498bf133" xlink:to="loc_lgnd_ProceedsFromInvestorsFinancingActivities_019f8a34-0646-79e1-b0e2-b0ef42fa0bcc" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_019e40d0-8bc9-7f04-bcb5-d1608526dd90" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffectContinuingOperations_019e40d0-8bc9-7a75-8ce7-c0614ccc99ab" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffectContinuingOperations"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_019e40d0-8bc9-7f04-bcb5-d1608526dd90" xlink:to="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffectContinuingOperations_019e40d0-8bc9-7a75-8ce7-c0614ccc99ab" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffectDisposalGroupIncludingDiscontinuedOperations_019e40d0-8bc9-763b-a2c6-16f4e4544354" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffectDisposalGroupIncludingDiscontinuedOperations"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_019e40d0-8bc9-7f04-bcb5-d1608526dd90" xlink:to="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffectDisposalGroupIncludingDiscontinuedOperations_019e40d0-8bc9-763b-a2c6-16f4e4544354" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffectContinuingOperations_019e40d0-8bc9-74bf-a052-5ef5e71e1dc6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffectContinuingOperations"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-722f-89d7-09d7335de4d2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffectContinuingOperations_019e40d0-8bc9-74bf-a052-5ef5e71e1dc6" xlink:to="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019e40d0-8bc9-722f-89d7-09d7335de4d2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019e40d0-8bc9-7673-8520-55def38b3b9c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffectContinuingOperations_019e40d0-8bc9-74bf-a052-5ef5e71e1dc6" xlink:to="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019e40d0-8bc9-7673-8520-55def38b3b9c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019e40d0-8bc9-79fd-83f6-18a50b5e6faf" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffectContinuingOperations_019e40d0-8bc9-74bf-a052-5ef5e71e1dc6" xlink:to="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019e40d0-8bc9-79fd-83f6-18a50b5e6faf" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_019e40d0-8bc9-7f18-96a3-d66b19de67d0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffectContinuingOperations_019e40d0-8bc9-74bf-a052-5ef5e71e1dc6" xlink:to="loc_us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_019e40d0-8bc9-7f18-96a3-d66b19de67d0" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019e40d0-8bc9-7ac4-bfc0-40d505262d51" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PaymentsToAcquireFinancialRoyaltyAssets_019e40d0-8bc9-7116-ad19-049b9177c092" xlink:href="lgnd-20260630.xsd#lgnd_PaymentsToAcquireFinancialRoyaltyAssets"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019e40d0-8bc9-7ac4-bfc0-40d505262d51" xlink:to="loc_lgnd_PaymentsToAcquireFinancialRoyaltyAssets_019e40d0-8bc9-7116-ad19-049b9177c092" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ProceedsFromFinancialRoyaltyAssets_019e40d0-8bc9-75e1-8136-193acc52b380" xlink:href="lgnd-20260630.xsd#lgnd_ProceedsFromFinancialRoyaltyAssets"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019e40d0-8bc9-7ac4-bfc0-40d505262d51" xlink:to="loc_lgnd_ProceedsFromFinancialRoyaltyAssets_019e40d0-8bc9-75e1-8136-193acc52b380" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForDerivativeInstrumentInvestingActivities_019e40d0-8bc9-7308-b249-0aa75f4967b4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsForDerivativeInstrumentInvestingActivities"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019e40d0-8bc9-7ac4-bfc0-40d505262d51" xlink:to="loc_us-gaap_PaymentsForDerivativeInstrumentInvestingActivities_019e40d0-8bc9-7308-b249-0aa75f4967b4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromDerivativeInstrumentInvestingActivities_019e40d0-8bc9-79c5-b927-c05602fd5d93" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ProceedsFromDerivativeInstrumentInvestingActivities"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019e40d0-8bc9-7ac4-bfc0-40d505262d51" xlink:to="loc_us-gaap_ProceedsFromDerivativeInstrumentInvestingActivities_019e40d0-8bc9-79c5-b927-c05602fd5d93" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_019e40d0-8bc9-7048-b540-74f57c4f2b60" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment"/>
    <link:calculationArc order="5" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019e40d0-8bc9-7ac4-bfc0-40d505262d51" xlink:to="loc_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_019e40d0-8bc9-7048-b540-74f57c4f2b60" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireShortTermInvestments_019e40d0-8bc9-7938-89a2-607008e1e731" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsToAcquireShortTermInvestments"/>
    <link:calculationArc order="6" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019e40d0-8bc9-7ac4-bfc0-40d505262d51" xlink:to="loc_us-gaap_PaymentsToAcquireShortTermInvestments_019e40d0-8bc9-7938-89a2-607008e1e731" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromSaleOfShortTermInvestments_019e40d0-8bc9-79d2-aa04-a04af81a25b0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ProceedsFromSaleOfShortTermInvestments"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019e40d0-8bc9-7ac4-bfc0-40d505262d51" xlink:to="loc_us-gaap_ProceedsFromSaleOfShortTermInvestments_019e40d0-8bc9-79d2-aa04-a04af81a25b0" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfShorttermInvestments_019e40d0-8bc9-7b23-9527-ccda56da4d2d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfShorttermInvestments"/>
    <link:calculationArc order="8" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019e40d0-8bc9-7ac4-bfc0-40d505262d51" xlink:to="loc_us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfShorttermInvestments_019e40d0-8bc9-7b23-9527-ccda56da4d2d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireOtherInvestments_019f8a31-af61-795e-b82a-54b4b9c78073" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsToAcquireOtherInvestments"/>
    <link:calculationArc order="9" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019e40d0-8bc9-7ac4-bfc0-40d505262d51" xlink:to="loc_us-gaap_PaymentsToAcquireOtherInvestments_019f8a31-af61-795e-b82a-54b4b9c78073" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesInvestmentCategoriesDetails" xlink:type="simple" xlink:href="lgnd-20260630.xsd#BasisofPresentationandSummaryofSignificantAccountingPoliciesInvestmentCategoriesDetails"/>
  <link:calculationLink xlink:role="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesInvestmentCategoriesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_019e40d0-8bc9-7679-9006-85644d5251ae" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_019e40d0-8bc9-74e3-a2ab-1c3c099196f7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_019e40d0-8bc9-7679-9006-85644d5251ae" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_019e40d0-8bc9-74e3-a2ab-1c3c099196f7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_019e40d0-8bc9-7c56-9dd3-6bbc95170267" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_019e40d0-8bc9-7679-9006-85644d5251ae" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_019e40d0-8bc9-7c56-9dd3-6bbc95170267" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_019e40d0-8bc9-7c06-b475-9cacedb37885" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_019e40d0-8bc9-7679-9006-85644d5251ae" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_019e40d0-8bc9-7c06-b475-9cacedb37885" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesAvailableforSaleDebtSecuritiesbyContractualMaturityDetails" xlink:type="simple" xlink:href="lgnd-20260630.xsd#BasisofPresentationandSummaryofSignificantAccountingPoliciesAvailableforSaleDebtSecuritiesbyContractualMaturityDetails"/>
  <link:calculationLink xlink:role="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesAvailableforSaleDebtSecuritiesbyContractualMaturityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesSingleMaturityDate_019e40d0-8ca3-7b3d-9b38-49df525c389f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesSingleMaturityDate"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesNextRollingTwelveMonthsFairValue_019e40d0-8ca3-784f-86ed-e317dc452068" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesNextRollingTwelveMonthsFairValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesSingleMaturityDate_019e40d0-8ca3-7b3d-9b38-49df525c389f" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesNextRollingTwelveMonthsFairValue_019e40d0-8ca3-784f-86ed-e317dc452068" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesRollingYearTwoThroughFiveFairValue_019e40d0-8ca3-76e8-8d67-ae1bb2ad7d44" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesRollingYearTwoThroughFiveFairValue"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesSingleMaturityDate_019e40d0-8ca3-7b3d-9b38-49df525c389f" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesRollingYearTwoThroughFiveFairValue_019e40d0-8ca3-76e8-8d67-ae1bb2ad7d44" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_HeldToMaturitySecuritiesDebtMaturitiesSingleMaturityDateAmortizedCostBasis_019e40d0-8ca3-715c-b164-59edba6e27c1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_HeldToMaturitySecuritiesDebtMaturitiesSingleMaturityDateAmortizedCostBasis"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesNextRollingTwelveMonthsAmortizedCostBasis_019e40d0-8ca3-7101-9f70-2758683d4393" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesNextRollingTwelveMonthsAmortizedCostBasis"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_HeldToMaturitySecuritiesDebtMaturitiesSingleMaturityDateAmortizedCostBasis_019e40d0-8ca3-715c-b164-59edba6e27c1" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesNextRollingTwelveMonthsAmortizedCostBasis_019e40d0-8ca3-7101-9f70-2758683d4393" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesRollingYearTwoThroughFiveAmortizedCostBasis_019e40d0-8ca3-79e4-8860-eaf6d5cbaa2a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesRollingYearTwoThroughFiveAmortizedCostBasis"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_HeldToMaturitySecuritiesDebtMaturitiesSingleMaturityDateAmortizedCostBasis_019e40d0-8ca3-715c-b164-59edba6e27c1" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesRollingYearTwoThroughFiveAmortizedCostBasis_019e40d0-8ca3-79e4-8860-eaf6d5cbaa2a" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesGoodwillandOtherIdentifiableIntangibleAssetsDetails" xlink:type="simple" xlink:href="lgnd-20260630.xsd#BasisofPresentationandSummaryofSignificantAccountingPoliciesGoodwillandOtherIdentifiableIntangibleAssetsDetails"/>
  <link:calculationLink xlink:role="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesGoodwillandOtherIdentifiableIntangibleAssetsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IntangibleAssetsNetIncludingGoodwill_019e40d0-8ca3-7c88-b0a2-edcfcd4a5158" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IntangibleAssetsNetIncludingGoodwill"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Goodwill_019e40d0-8ca3-72be-91b6-398b5fc91b56" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_Goodwill"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_IntangibleAssetsNetIncludingGoodwill_019e40d0-8ca3-7c88-b0a2-edcfcd4a5158" xlink:to="loc_us-gaap_Goodwill_019e40d0-8ca3-72be-91b6-398b5fc91b56" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsNet_019e40d0-8ca3-738d-9622-26c575745022" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsNet"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_IntangibleAssetsNetIncludingGoodwill_019e40d0-8ca3-7c88-b0a2-edcfcd4a5158" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsNet_019e40d0-8ca3-738d-9622-26c575745022" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsNet_019e40d0-8ca3-7e8c-a0c4-87028d06dff7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsNet"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsGross_019e40d0-8ca3-74fb-affb-b3b132651e57" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsGross"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsNet_019e40d0-8ca3-7e8c-a0c4-87028d06dff7" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsGross_019e40d0-8ca3-74fb-affb-b3b132651e57" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_019e40d0-8ca3-7ce1-9f78-a83354bc63a2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsNet_019e40d0-8ca3-7e8c-a0c4-87028d06dff7" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_019e40d0-8ca3-7ce1-9f78-a83354bc63a2" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesOtherAssetsDetails" xlink:type="simple" xlink:href="lgnd-20260630.xsd#BasisofPresentationandSummaryofSignificantAccountingPoliciesOtherAssetsDetails"/>
  <link:calculationLink xlink:role="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesOtherAssetsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsNoncurrent_019e40d0-8ca3-7a65-b159-439733f9a76e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherAssetsNoncurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseRightOfUseAsset_019e40d0-8ca3-7d7c-82a8-33347eef388a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingLeaseRightOfUseAsset"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OtherAssetsNoncurrent_019e40d0-8ca3-7a65-b159-439733f9a76e" xlink:to="loc_us-gaap_OperatingLeaseRightOfUseAsset_019e40d0-8ca3-7d7c-82a8-33347eef388a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_019e40d0-8ca3-7674-982b-814ff54c9dec" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OtherAssetsNoncurrent_019e40d0-8ca3-7a65-b159-439733f9a76e" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentNet_019e40d0-8ca3-7674-982b-814ff54c9dec" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_Other_019e40d0-8ca3-794b-b1cb-808ac08dad8c" xlink:href="lgnd-20260630.xsd#lgnd_Other"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OtherAssetsNoncurrent_019e40d0-8ca3-7a65-b159-439733f9a76e" xlink:to="loc_lgnd_Other_019e40d0-8ca3-794b-b1cb-808ac08dad8c" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesAccruedLiabilitiesDetails" xlink:type="simple" xlink:href="lgnd-20260630.xsd#BasisofPresentationandSummaryofSignificantAccountingPoliciesAccruedLiabilitiesDetails"/>
  <link:calculationLink xlink:role="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesAccruedLiabilitiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesCurrent_019e40d0-8ca3-727a-b747-8e018f8381b0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccruedLiabilitiesCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedRoyaltiesCurrentAndNoncurrent_019e40d0-8ca3-79cd-b15f-ee9868c99cbb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccruedRoyaltiesCurrentAndNoncurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_019e40d0-8ca3-727a-b747-8e018f8381b0" xlink:to="loc_us-gaap_AccruedRoyaltiesCurrentAndNoncurrent_019e40d0-8ca3-79cd-b15f-ee9868c99cbb" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeRelatedLiabilitiesCurrent_019e40d0-8ca3-7a11-b551-06f8047dc77f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeRelatedLiabilitiesCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_019e40d0-8ca3-727a-b747-8e018f8381b0" xlink:to="loc_us-gaap_EmployeeRelatedLiabilitiesCurrent_019e40d0-8ca3-7a11-b551-06f8047dc77f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedProfessionalFeesCurrent_019e40d0-8ca3-7cdc-92e1-87685465b763" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccruedProfessionalFeesCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_019e40d0-8ca3-727a-b747-8e018f8381b0" xlink:to="loc_us-gaap_AccruedProfessionalFeesCurrent_019e40d0-8ca3-7cdc-92e1-87685465b763" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestPayableCurrent_019e40d0-8ca3-73e1-a853-01555fa9140c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InterestPayableCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_019e40d0-8ca3-727a-b747-8e018f8381b0" xlink:to="loc_us-gaap_InterestPayableCurrent_019e40d0-8ca3-73e1-a853-01555fa9140c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ValueAddedTaxReceivableNetCurrent_019e40d0-8ca3-7032-b2df-2dad45a81612" xlink:href="lgnd-20260630.xsd#lgnd_ValueAddedTaxReceivableNetCurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_019e40d0-8ca3-727a-b747-8e018f8381b0" xlink:to="loc_lgnd_ValueAddedTaxReceivableNetCurrent_019e40d0-8ca3-7032-b2df-2dad45a81612" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AccruedSubcontractorExpensesCurrent_019e40d0-8ca3-70e1-88be-a52978763914" xlink:href="lgnd-20260630.xsd#lgnd_AccruedSubcontractorExpensesCurrent"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_019e40d0-8ca3-727a-b747-8e018f8381b0" xlink:to="loc_lgnd_AccruedSubcontractorExpensesCurrent_019e40d0-8ca3-70e1-88be-a52978763914" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_019e40d0-8ca3-7544-b294-02814369f86f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_019e40d0-8ca3-727a-b747-8e018f8381b0" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_019e40d0-8ca3-7544-b294-02814369f86f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAccruedLiabilitiesCurrent_019e40d0-8ca3-75b6-90a7-6e2b3a3f91ec" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherAccruedLiabilitiesCurrent"/>
    <link:calculationArc order="8" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_019e40d0-8ca3-727a-b747-8e018f8381b0" xlink:to="loc_us-gaap_OtherAccruedLiabilitiesCurrent_019e40d0-8ca3-75b6-90a7-6e2b3a3f91ec" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesOtherLongtermLiabilitiesDetails" xlink:type="simple" xlink:href="lgnd-20260630.xsd#BasisofPresentationandSummaryofSignificantAccountingPoliciesOtherLongtermLiabilitiesDetails"/>
  <link:calculationLink xlink:role="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesOtherLongtermLiabilitiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesNoncurrent_019e40d0-8ca3-7c68-b28c-234d86ba4c1e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherLiabilitiesNoncurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnrecognizedTaxBenefits_019e40d0-8ca3-7dc4-afbf-ceb70ec8f86e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_UnrecognizedTaxBenefits"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OtherLiabilitiesNoncurrent_019e40d0-8ca3-7c68-b28c-234d86ba4c1e" xlink:to="loc_us-gaap_UnrecognizedTaxBenefits_019e40d0-8ca3-7dc4-afbf-ceb70ec8f86e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherSundryLiabilitiesNoncurrent_019e40d0-8ca3-7823-8bc8-538542ec6415" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherSundryLiabilitiesNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OtherLiabilitiesNoncurrent_019e40d0-8ca3-7c68-b28c-234d86ba4c1e" xlink:to="loc_us-gaap_OtherSundryLiabilitiesNoncurrent_019e40d0-8ca3-7823-8bc8-538542ec6415" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesNetLossGainPerShareDetails" xlink:type="simple" xlink:href="lgnd-20260630.xsd#BasisofPresentationandSummaryofSignificantAccountingPoliciesNetLossGainPerShareDetails"/>
  <link:calculationLink xlink:role="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesNetLossGainPerShareDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_019e40d0-8ca3-7514-883d-24be2205e40a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_019e40d0-8ca3-7a6f-9977-60eab0bc81da" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_019e40d0-8ca3-7514-883d-24be2205e40a" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_019e40d0-8ca3-7a6f-9977-60eab0bc81da" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_019e40d0-8ca3-7570-b8ff-bb8ee0f6a977" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_019e40d0-8ca3-7514-883d-24be2205e40a" xlink:to="loc_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_019e40d0-8ca3-7570-b8ff-bb8ee0f6a977" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities_019e40d0-8ca3-797b-ad45-2ad482c92b3a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_019e40d0-8ca3-7514-883d-24be2205e40a" xlink:to="loc_us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities_019e40d0-8ca3-797b-ad45-2ad482c92b3a" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ligand.com/role/FinancialRoyaltyAssetsnetScheduleofFinancialRoyaltyAssetsDetails" xlink:type="simple" xlink:href="lgnd-20260630.xsd#FinancialRoyaltyAssetsnetScheduleofFinancialRoyaltyAssetsDetails"/>
  <link:calculationLink xlink:role="http://www.ligand.com/role/FinancialRoyaltyAssetsnetScheduleofFinancialRoyaltyAssetsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FinancialRoyaltyAssetsNet_019e40d0-8ca4-7b05-a2c8-67eaad0bdb3b" xlink:href="lgnd-20260630.xsd#lgnd_FinancialRoyaltyAssetsNet"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FinancialRoyaltyAssetsGross_019e40d0-8ca4-7467-97f2-4f7521c12df3" xlink:href="lgnd-20260630.xsd#lgnd_FinancialRoyaltyAssetsGross"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_lgnd_FinancialRoyaltyAssetsNet_019e40d0-8ca4-7b05-a2c8-67eaad0bdb3b" xlink:to="loc_lgnd_FinancialRoyaltyAssetsGross_019e40d0-8ca4-7467-97f2-4f7521c12df3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FinancialRoyaltyAssetsAllowance_019e40d0-8ca4-7747-9889-88bf352d7438" xlink:href="lgnd-20260630.xsd#lgnd_FinancialRoyaltyAssetsAllowance"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_lgnd_FinancialRoyaltyAssetsNet_019e40d0-8ca4-7b05-a2c8-67eaad0bdb3b" xlink:to="loc_lgnd_FinancialRoyaltyAssetsAllowance_019e40d0-8ca4-7747-9889-88bf352d7438" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ligand.com/role/FairValueMeasurementsAssetsandLiabilitiesMeasuredatFairValueonRecurringBasisDetails" xlink:type="simple" xlink:href="lgnd-20260630.xsd#FairValueMeasurementsAssetsandLiabilitiesMeasuredatFairValueonRecurringBasisDetails"/>
  <link:calculationLink xlink:role="http://www.ligand.com/role/FairValueMeasurementsAssetsandLiabilitiesMeasuredatFairValueonRecurringBasisDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesFairValueDisclosure_019e40d0-8ca4-762b-a609-6898074a11c5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LiabilitiesFairValueDisclosure"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeLiabilities_019e40d0-8ca4-7571-9f05-e29ced1dd6a5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DerivativeLiabilities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesFairValueDisclosure_019e40d0-8ca4-762b-a609-6898074a11c5" xlink:to="loc_us-gaap_DerivativeLiabilities_019e40d0-8ca4-7571-9f05-e29ced1dd6a5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationContingentConsiderationLiabilityFairValueDisclosure_019e40d0-8ca4-7125-a411-c840e9b788c5" xlink:href="lgnd-20260630.xsd#lgnd_BusinessCombinationContingentConsiderationLiabilityFairValueDisclosure"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesFairValueDisclosure_019e40d0-8ca4-762b-a609-6898074a11c5" xlink:to="loc_lgnd_BusinessCombinationContingentConsiderationLiabilityFairValueDisclosure_019e40d0-8ca4-7125-a411-c840e9b788c5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_019e40d0-8ca4-74f0-abe6-1f7a50b65445" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentsFairValueDisclosure_019e40d0-8ca4-7f42-87f1-a24b4ced214d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InvestmentsFairValueDisclosure"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsFairValueDisclosure_019e40d0-8ca4-74f0-abe6-1f7a50b65445" xlink:to="loc_us-gaap_InvestmentsFairValueDisclosure_019e40d0-8ca4-7f42-87f1-a24b4ced214d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquitySecuritiesFvNiCurrentAndNoncurrent_019e40d0-8ca4-70cf-9a8d-dd4a0be2d7aa" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquitySecuritiesFvNiCurrentAndNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsFairValueDisclosure_019e40d0-8ca4-74f0-abe6-1f7a50b65445" xlink:to="loc_us-gaap_EquitySecuritiesFvNiCurrentAndNoncurrent_019e40d0-8ca4-70cf-9a8d-dd4a0be2d7aa" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeAssets_019e40d0-8ca4-7b66-b382-27453be3fc57" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DerivativeAssets"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsFairValueDisclosure_019e40d0-8ca4-74f0-abe6-1f7a50b65445" xlink:to="loc_us-gaap_DerivativeAssets_019e40d0-8ca4-7b66-b382-27453be3fc57" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.ligand.com/role/DebtConvertibleDebtScheduleDetails" xlink:type="simple" xlink:href="lgnd-20260630.xsd#DebtConvertibleDebtScheduleDetails"/>
  <link:calculationLink xlink:role="http://www.ligand.com/role/DebtConvertibleDebtScheduleDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_019e40d0-8ca4-7394-82cd-6ee697286cda" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongTermDebt"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentCarryingAmount_019e40d0-8ca4-7b97-b45d-6d51ccb98a24" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentCarryingAmount"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LongTermDebt_019e40d0-8ca4-7394-82cd-6ee697286cda" xlink:to="loc_us-gaap_DebtInstrumentCarryingAmount_019e40d0-8ca4-7b97-b45d-6d51ccb98a24" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet_019e40d0-8ca4-712d-8193-4a18af1c5af2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LongTermDebt_019e40d0-8ca4-7394-82cd-6ee697286cda" xlink:to="loc_us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet_019e40d0-8ca4-712d-8193-4a18af1c5af2" xlink:type="arc"/>
  </link:calculationLink>
</link:linkbase>
