BACKGROUND: The concomitant use of proton pump inhibitors (PPIs) with clopidogrel is suspected to be associated with an adverse impact on clinical outcomes in patients with coronary artery disease. We sought to evaluate whether the use of PPIs with clopidogrel was associated with worse clinical outcomes after percutaneous coronary intervention (PCI) compared with the use of clopidogrel alone. METHODS AND RESULTS: We studied 2651 consecutive patients discharged alive after coronary stenting for stable or unstable coronary artery disease between 2001 and 2007. All patients received aspirin indefinitely and a thienopyridine for 1 to 12 months. Patients were categorized into 2 groups: those taking a PPI [PPI (+), n=751] and those not taking a PPI [PPI (-), n=1900] at discharge. The primary end points were the 6-month incidence of major adverse cardiovascular events (MACE) (composite of death, myocardial infarction, target vessel revascularization, and stent thrombosis) and net adverse clinical events (NACE) (composite of MACE and thrombolysis in myocardial infarction major or minor bleeding), which were evaluated using propensity-adjusted Cox regression analysis. In addition, propensity-matched analysis was performed in 685 pairs of patients. The PPI (+) group was older and had more comorbid conditions than the PPI (-) group. In propensity-adjusted as well as propensity-matched analyses, the use of PPIs was not associated with an increased risk of MACE or NACE. CONCLUSIONS: The use of PPIs with dual antiplatelet therapy was not associated with any adverse influence on MACE or NACE after PCI.