BACKGROUND: Selection of an appropriate antithrombotic regimen in patients requiring oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) still remains a challenge. An ideal 9-2regimen should balance the risk of bleeding against ischemic benefit. METHODS: A comprehensive literature search for studies comparing triple antithrombotic therapy (TAT) vs double antithrombotic therapy (DAT) in patients requiring OAC undergoing PCI was performed in clinicalTrials.gov, PubMed, Web of Science, EBSCO Services, Cochrane Central Register of Controlled Trials, Google Scholar, and various scientific conference sessions from inception to May 1st, 2019. A meta-analysis was performed using random-effects model to calculate risk ratio (RR) and 95% confidence interval (CI). RESULTS: Fifteen studies were eligible and included 13 967 patients, of which 7349 received TAT and 6618 received DAT. Compared with DAT, TAT was associated with lower risk of myocardial infarction (RR, 0.82; 95%CI, 0.69-0.98; P = .03) and stent thrombosis (RR, 0.66; 95%CI, 0.46-0.96; P = .03). There was no difference in risk of trial defined major adverse cardiac events, all-cause mortality, and stroke between two groups. Compared with DAT, TAT was associated with higher risk of trial defined major bleeding (RR, 1.67; 95%CI, 1.38-2.01; P < .00001), including thrombolysis in myocardial infarction major bleeding (RR, 1.81; 95%CI, 1.47-2.24; P < .00001) but no significant difference in risk of intracranial bleeding. CONCLUSION: In patients requiring OAC undergoing PCI, TAT was associated with a lower risk of myocardial infarction but with a significantly higher risk of major bleeding when compared with DAT.