Although it has been reported that prasugrel achieves stronger antiplatelet effect and fewer cardiovascular events compared to clopidogrel in Japanese patients, there are limited data comparing the safety between the 2 dose regimens. Data from 1031 consecutive patients with coronary artery disease undergoing PCI at 5 institutions from May 2014 to April 2016, who received aspirin plus either clopidogrel (619 patients) or prasugrel (412 patients), were retrospectively analyzed. The choice of clopidogrel or prasugrel was left to the operator's discretion. Adverse events were defined as a composite of bleeding, hepatopathy, leukopenia, thrombopenia, exanthema, and major adverse cardiovascular events (MACE). MACE was defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal ischemic stroke. The average follow-up period was 143 days in the prasugrel group and 263 days in the clopidogrel group. Adverse events occurred in 34.5% of patients in the prasugrel group and in 28.6% in the clopidogrel group. Although the Kaplan–Meier curves showed lower survival rates from MACE, all-bleeding, major bleeding, minor bleeding, and adverse events, in the prasugrel group compared to the clopidogrel group (log rank test p = 0.009, p = 0.001, p = 0.012, p = 0.018, and p < 0.001, respectively), multivariate Cox-regression analyses determined prasugrel as a significant risk factor for all-bleeding, minor bleeding, and adverse events, but not for MACE and major bleeding events. Dual antiplatelet therapy with prasugrel was independently associated with minor bleeding events, but not with MACE and major bleeding events, compared to clopidogrel, after PCI in common clinical settings.