Objective The main aim of this meta-analysis is to compare the efficacy and safety of dual versus single antiplatelet therapy for patients taking oral anticoagulation (OAC) after coronary intervention. Background The optimal regimen remains controversial patients taking OAC after coronary intervention. Methods PubMed, Embase and Cochrane Central Register of Controlled Trials were searched for eligible studies including data of triple therapy (TT) versus OAC plus single antiplatelet therapy for patients requiring OAC after coronary intervention. The primary outcome was major adverse cardiac and cerebrovascular event (MACCE). The safety outcome was major bleeding. Results Fourteen studies with 32825 patients were included. Among prospective studies, patients with TT had a trend toward a higher risk of major bleeding [odds ratios (OR): 1.56, 95% confidence interval (CI): 0.98–2.49, P = 0.06] and a markedly higher risk of all-cause death (OR; 2.11, 95% CI: 1.10–4.06 P = 0.02) compared with OAC plus clopidogrel. Meanwhile, TT was associated with decreased risks of MACCE (OR: 0.63, 95% CI: 051–0.77 P P = 0.04), and stroke/transient ischemic attack (TIA)/peripheral embolism (PE) (OR: 0.29, 95% CI: 0.09–0.96, P = 0.04) compared with OAC plus aspirin.