To compare the efficacy and safety of dual antiplatelet therapy (DAPT) and triple therapy (TT, dual antiplatelet plus warfarin) in patients with myocardial infarction (MI) or PCI with stenting (PCI‐S) who also require chronic oral anticoagulation. Background: Recommendations for the optimal antiplatelet/anticoagulant treatment regimen for patients undergoing PCI‐S or MI who also require oral anticoagulation are largely based on evidence from observational studies and expert opinions. Methods: A systematic search was performed for studies comparing TT vs. DAPT in patients post PCI‐S or MI and requiring chronic anticoagulation. Primary outcome was all‐cause mortality. Secondary outcomes were ischemic stroke, major bleeding, MI, and stent thrombosis. Pooled relative risks (RR) were calculated using random effects model. Results: A total of 17 studies were included, with 14,921 patients [TT: 5,819(39%) and DAPT: 9,102(61%)] and a mean follow‐up of 1.6 years. The majority of patients required oral anticoagulation for atrial fibrillation. Compared to DAPT, patients treated with TT had no significant difference in all‐cause mortality [RR: 0.81, 95% confidence interval (CI): 0.61–1.08, P = 0.15], MI [RR 0.74, 95% CI: 0.51–1.06, P = 0.10], and stent thrombosis [RR 0.67, 95% CI: 0.35–1.30, P = 0.24]. Patients treated with TT had significantly increased risk of major bleeding [RR 1.20, 95% CI: 1.03–1.39, P = 0.02], whereas the risk for ischemic stroke was significantly lower [RR 0.59, 95% CI: 0.38‐0.92, P = 0.02]. Conclusions: All‐cause mortality appears similar in patients treated with TT or DAPT although TT was associated with higher rates of major bleeding and a lower risk for ischemic stroke. © 2015 Wiley Periodicals, Inc.