Background: Proton pump inhibitors (PPIs) are commonly prescribed medications that are thought to increase the risk of cardiovascular events because they reduce the effectiveness of clopidogrel via shared hepatic pathways. Objective: This study examined the prevalence of concomitant prescribing of clopidogrel/PPI among patients diagnosed with acute coronary syndrome and the adverse cardiovascular event associated with this interaction. Methods: A retrospective cohort study was conducted by retrieving patient data from the Nat Health Insurance claims processor database in Palestine. Adults diagnosed with Acute Coronary Syndrome (ACS) from 2019 through 2021 who were prescribed clopidogrel or clopidogrel in combination with a PPI were included in the study. Endpoints were adverse cardiac events, including readmission for revascularization during the first year of treatment. Results:The study included 443 patients; the prevalence of prescribing concomitant clopidogrel with a PPI was 74.7%, whereas 49.2% were prescribed interacting PPI (omeprazole, esomeprazole, and lansoprazole). 59 (13.3%) of participants experienced a cardiovascular event within 1 year of starting therapy, including 27 (12.4%) patients who had a cardiovascular event while taking an interacting PPI. No significant association was found between PPI administration and increased CV event risk in patients receiving concomitant clopidogrel and PPIs therapy (p = 0.579). Conclusion:In this study, we observed a high prevalence of prescribing a PPI in combination with clopidogrel, regardless of the FDA recommendations. No significant increase in cardiovascular events was observed in patients receiving concomitant clopidogrel and PPI therapy.