This meta-analysis explores the efficacy and safety of dual antithrombotic treatment (DAT); novel oral anticoagulants (NOAC)-based triple antithrombotic therapy (TAT); vitamin K antagonist (VKA)-based TAT in patients with AF undergoing PCI. Relevant studies listed in English in PubMed, Google Scholar, the Cochrane Library, or ClinicalTrials.gov were identified. We used a random effects model to calculate odds ratios (OR) and 95% confidence intervals (CI). Endpoints included all bleeding events, intracranial hemorrhage, cardiac death, all-cause death, myocardial infarction (MI), stent thrombosis (ST), stroke, and major adverse cardiac events (MACEs). There were 6918 participants in all relevant trials, DAT showed superiority over TAT in reducing the risks of Thrombolysis in Myocardial infarction (TIMI) major bleeding (OR: 1.71, 95% CI: 1.12, 2.62), TIMI major or minor bleeding(OR: 1.75, 95%CI: 1.13, 2.71), International Society on Thrombosis and Hemostasis (ISTH) major bleeding (OR: 1.42, 95% CI: 1.03, 1.96), and Intracranial haemorrhage(OR: 2.44, 95% CI: 1.21, 4.90). In a mutual comparison of three antithrombotic regimens, NOAC-based TAT showed no statistical difference with DAT. VKA-based TAT enlarged the risk of all bleeding events relative to DAT. DAT reduced highly the risk of bleeding events. DAT and VKA-based TAT had similar efficacy outcomes. There was no statistical difference of safety and efficacy between NOAC-based TAT and DAT.