Clopidogrel requires activation to have antiplatelet effects. Pharmacogenetic testing to identify patients with impaired function can be coupled with clinical decision support (CDS) alerts to guide antiplatelet prescribing. We evaluated the impact of alerts on clopidogrel prescribing. We retrospectively analyzed data for 866 patients in which -clopidogrel CDS was deployed at a single healthcare system during 2015-2023. Analyses included 2,288 alerts. CDS acceptance rates increased from 24% in 2015 to 63% in 2023 ( < 0.05). Adjusted analyses also showed higher acceptance rates when clopidogrel had been ordered for a percutaneous intervention (OR: 28.7, < 0.001) and when cardiologists responded to alerts (OR: 2.11, = 0.001). CDS for -clopidogrel was effective in reducing potential drug-gene interactions. Its influence varied by clinician specialty and medication indications.