<?xml version="1.0" encoding="UTF-8"?>
<!--XBRL Document Modified with Ez-Editor Version 1.6.0.0 on Thursday, August 04, 2016 08:27:51 PM -->
<linkbase xmlns="http://www.xbrl.org/2003/linkbase" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xlink="http://www.w3.org/1999/xlink" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
<roleRef xlink:type="simple" xlink:href="oprx-20160630.xsd#CondensedConsolidatedBalanceSheetsUnaudited" roleURI="http://OPRX/role/CondensedConsolidatedBalanceSheetsUnaudited"/>
<calculationLink xlink:type="extended" xlink:role="http://OPRX/role/CondensedConsolidatedBalanceSheetsUnaudited">
<loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AssetsCurrent" xlink:label="loc_us-gaap_AssetsCurrent"/>
<loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
<calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue" order="10" use="optional" weight="1"/>
<loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AccountsReceivableNetCurrent" xlink:label="loc_us-gaap_AccountsReceivableNetCurrent"/>
<calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent" xlink:to="loc_us-gaap_AccountsReceivableNetCurrent" order="20" use="optional" weight="1"/>
<loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_PrepaidExpenseCurrent" xlink:label="loc_us-gaap_PrepaidExpenseCurrent"/>
<calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent" xlink:to="loc_us-gaap_PrepaidExpenseCurrent" order="30" use="optional" weight="1"/>
<loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_OtherAssets" xlink:label="loc_us-gaap_OtherAssets"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsNet" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsNet"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OtherAssets" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsNet" order="10" use="optional" weight="1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_CapitalizedComputerSoftwareNet" xlink:label="loc_us-gaap_CapitalizedComputerSoftwareNet"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OtherAssets" xlink:to="loc_us-gaap_CapitalizedComputerSoftwareNet" order="20" use="optional" weight="1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_SecurityDeposit" xlink:label="loc_us-gaap_SecurityDeposit"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OtherAssets" xlink:to="loc_us-gaap_SecurityDeposit" order="30" use="optional" weight="1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_Assets" xlink:label="loc_us-gaap_Assets"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets" xlink:to="loc_us-gaap_AssetsCurrent" order="10" use="optional" weight="1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentNet" order="20" use="optional" weight="1"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets" xlink:to="loc_us-gaap_OtherAssets" order="30" use="optional" weight="1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_LiabilitiesCurrent" xlink:label="loc_us-gaap_LiabilitiesCurrent"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AccountsPayableTradeCurrent" xlink:label="loc_us-gaap_AccountsPayableTradeCurrent"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent" xlink:to="loc_us-gaap_AccountsPayableTradeCurrent" order="10" use="optional" weight="1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AccountsPayableRelatedPartiesCurrent" xlink:label="loc_us-gaap_AccountsPayableRelatedPartiesCurrent"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent" xlink:to="loc_us-gaap_AccountsPayableRelatedPartiesCurrent" order="20" use="optional" weight="1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:label="loc_us-gaap_AccruedLiabilitiesCurrent"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent" xlink:to="loc_us-gaap_AccruedLiabilitiesCurrent" order="30" use="optional" weight="1"/><loc xlink:type="locator" xlink:href="oprx-20160630.xsd#oprx_RevenueSharePayableCurrent" xlink:label="loc_oprx_RevenueSharePayableCurrent"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent" xlink:to="loc_oprx_RevenueSharePayableCurrent" order="40" use="optional" weight="1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_DeferredRevenueCurrent" xlink:label="loc_us-gaap_DeferredRevenueCurrent"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent" xlink:to="loc_us-gaap_DeferredRevenueCurrent" order="50" use="optional" weight="1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_StockholdersEquity" xlink:label="loc_us-gaap_StockholdersEquity"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_CommonStockValue" xlink:label="loc_us-gaap_CommonStockValue"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity" xlink:to="loc_us-gaap_CommonStockValue" order="10" use="optional" weight="1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_PreferredStockValue" xlink:label="loc_us-gaap_PreferredStockValue"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity" xlink:to="loc_us-gaap_PreferredStockValue" order="20" use="optional" weight="1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_WarrantsAndRightsOutstanding" xlink:label="loc_us-gaap_WarrantsAndRightsOutstanding"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity" xlink:to="loc_us-gaap_WarrantsAndRightsOutstanding" order="30" use="optional" weight="1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AdditionalPaidInCapital" xlink:label="loc_us-gaap_AdditionalPaidInCapital"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity" xlink:to="loc_us-gaap_AdditionalPaidInCapital" order="40" use="optional" weight="1"/><loc xlink:type="locator" xlink:href="oprx-20160630.xsd#oprx_StockPayable" xlink:label="loc_oprx_StockPayable"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity" xlink:to="loc_oprx_StockPayable" order="50" use="optional" weight="1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_DeferredCompensationEquity" xlink:label="loc_us-gaap_DeferredCompensationEquity"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity" xlink:to="loc_us-gaap_DeferredCompensationEquity" order="60" use="optional" weight="-1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_RetainedEarningsAccumulatedDeficit" xlink:label="loc_us-gaap_RetainedEarningsAccumulatedDeficit"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity" xlink:to="loc_us-gaap_RetainedEarningsAccumulatedDeficit" order="70" use="optional" weight="1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:label="loc_us-gaap_LiabilitiesAndStockholdersEquity"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="loc_us-gaap_LiabilitiesCurrent" order="10" use="optional" weight="1"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="loc_us-gaap_StockholdersEquity" order="20" use="optional" weight="1"/></calculationLink>





<roleRef xlink:type="simple" xlink:href="oprx-20160630.xsd#CondensedConsolidatedStatementsOfOperationsUnaudited" roleURI="http://OPRX/role/CondensedConsolidatedStatementsOfOperationsUnaudited"/>
<calculationLink xlink:type="extended" xlink:role="http://OPRX/role/CondensedConsolidatedStatementsOfOperationsUnaudited">
<loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_GrossProfit" xlink:label="loc_us-gaap_GrossProfit"/>
<loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_Revenues" xlink:label="loc_us-gaap_Revenues"/>
<calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_GrossProfit" xlink:to="loc_us-gaap_Revenues" order="10" use="optional" weight="1"/>
<loc xlink:type="locator" xlink:href="oprx-20160630.xsd#oprx_RevenueShareExpense" xlink:label="loc_oprx_RevenueShareExpense"/>
<calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_GrossProfit" xlink:to="loc_oprx_RevenueShareExpense" order="20" use="optional" weight="-1"/>
<loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_OperatingIncomeLoss" xlink:label="loc_us-gaap_OperatingIncomeLoss"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss" xlink:to="loc_us-gaap_GrossProfit" order="10" use="optional" weight="1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_OperatingExpenses" xlink:label="loc_us-gaap_OperatingExpenses"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss" xlink:to="loc_us-gaap_OperatingExpenses" order="20" use="optional" weight="-1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_NonoperatingIncomeExpense" xlink:label="loc_us-gaap_NonoperatingIncomeExpense"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_InterestAndOtherIncome" xlink:label="loc_us-gaap_InterestAndOtherIncome"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NonoperatingIncomeExpense" xlink:to="loc_us-gaap_InterestAndOtherIncome" order="10" use="optional" weight="1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_InterestExpense" xlink:label="loc_us-gaap_InterestExpense"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NonoperatingIncomeExpense" xlink:to="loc_us-gaap_InterestExpense" order="20" use="optional" weight="-1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:to="loc_us-gaap_OperatingIncomeLoss" order="10" use="optional" weight="1"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:to="loc_us-gaap_NonoperatingIncomeExpense" order="20" use="optional" weight="1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="loc_us-gaap_NetIncomeLoss"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" order="10" use="optional" weight="1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IncomeTaxExpenseBenefit" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit" order="20" use="optional" weight="-1"/></calculationLink>




<roleRef xlink:type="simple" xlink:href="oprx-20160630.xsd#CondensedConsolidatedStatementsOfCashFlowsUnaudited" roleURI="http://OPRX/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"/>
<calculationLink xlink:type="extended" xlink:role="http://OPRX/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited">
<loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
<loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="loc_us-gaap_NetIncomeLoss"/>
<calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="loc_us-gaap_NetIncomeLoss" order="10" use="optional" weight="1"/>
<loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_DepreciationAndAmortization" xlink:label="loc_us-gaap_DepreciationAndAmortization"/>
<calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="loc_us-gaap_DepreciationAndAmortization" order="20" use="optional" weight="1"/>
<loc xlink:type="locator" xlink:href="oprx-20160630.xsd#oprx_StockOptionsIssuedForServices" xlink:label="loc_oprx_StockOptionsIssuedForServices"/>
<calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="loc_oprx_StockOptionsIssuedForServices" order="30" use="optional" weight="1"/>
<loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsReceivable" xlink:label="loc_us-gaap_IncreaseDecreaseInAccountsReceivable"/>
<calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="loc_us-gaap_IncreaseDecreaseInAccountsReceivable" order="40" use="optional" weight="-1"/>
<loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IncreaseDecreaseInPrepaidExpense" xlink:label="loc_us-gaap_IncreaseDecreaseInPrepaidExpense"/>
<calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="loc_us-gaap_IncreaseDecreaseInPrepaidExpense" order="50" use="optional" weight="-1"/>
<loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsPayable" xlink:label="loc_us-gaap_IncreaseDecreaseInAccountsPayable"/>
<calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="loc_us-gaap_IncreaseDecreaseInAccountsPayable" order="60" use="optional" weight="1"/>
<loc xlink:type="locator" xlink:href="oprx-20160630.xsd#oprx_IncreaseDecreaseInRevenueSharePayable" xlink:label="loc_oprx_IncreaseDecreaseInRevenueSharePayable"/>
<calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="loc_oprx_IncreaseDecreaseInRevenueSharePayable" order="70" use="optional" weight="-1"/>
<loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IncreaseDecreaseInAccruedLiabilities" xlink:label="loc_us-gaap_IncreaseDecreaseInAccruedLiabilities"/>
<calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="loc_us-gaap_IncreaseDecreaseInAccruedLiabilities" order="80" use="optional" weight="1"/>
<loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IncreaseDecreaseInDeferredRevenue" xlink:label="loc_us-gaap_IncreaseDecreaseInDeferredRevenue"/>
<calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="loc_us-gaap_IncreaseDecreaseInDeferredRevenue" order="90" use="optional" weight="1"/>
<loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:label="loc_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:to="loc_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" order="10" use="optional" weight="-1"/><loc xlink:type="locator" xlink:href="oprx-20160630.xsd#oprx_PaymentsToAcquirePatientRights" xlink:label="loc_oprx_PaymentsToAcquirePatientRights"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:to="loc_oprx_PaymentsToAcquirePatientRights" order="20" use="optional" weight="-1"/><loc xlink:type="locator" xlink:href="oprx-20160630.xsd#oprx_PaymentsToAcquireWebsiteDevelopment" xlink:label="loc_oprx_PaymentsToAcquireWebsiteDevelopment"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:to="loc_oprx_PaymentsToAcquireWebsiteDevelopment" order="30" use="optional" weight="-1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_PaymentsForRepurchaseOfCommonStock" xlink:label="loc_us-gaap_PaymentsForRepurchaseOfCommonStock"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:to="loc_us-gaap_PaymentsForRepurchaseOfCommonStock" order="10" use="optional" weight="-1"/><loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_CashAndCashEquivalentsPeriodIncreaseDecrease" xlink:label="loc_us-gaap_CashAndCashEquivalentsPeriodIncreaseDecrease"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashAndCashEquivalentsPeriodIncreaseDecrease" xlink:to="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities" order="10" use="optional" weight="1"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashAndCashEquivalentsPeriodIncreaseDecrease" xlink:to="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities" order="20" use="optional" weight="1"/><calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashAndCashEquivalentsPeriodIncreaseDecrease" xlink:to="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities" order="30" use="optional" weight="1"/></calculationLink>



</linkbase>
