Antithrombotic treatment in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) poses a dilemma. We compared outcomes of dual thrombotic therapy (DAT) (direct oral anticoagulants [DOACs]/warfarin + antiplatelets) versus triple antithrombotic therapy (TAT) (DOACs/warfarin, aspirin, and P2Y12 inhibitor) in this population. Multiple databases were searched from inception to 12/17/2023 to identify randomized controlled trials (RCTs) comparing DAT versus TAT in patients with AF and ACS. Outcomes included major adverse cardiac events (MACE), bleeding events, stroke, stent thrombosis, and myocardial infarction (MI). Relative risk (RR) and 95% confidence intervals were estimated with a random-effects model using the inverse-variance technique. We assigned I2>50% as an indicator of statistical heterogeneity. P-value <0.05 was considered significant. Ten RCTs comprising 6186 patients on TAT (female 26%, mean age 71±9 yrs) and 6,800 patients on DAT (female 27%, mean age 71±9 yrs) were included. Patients receiving DAT experienced lower rates of bleeding events compared to those receiving TAT, with relative risks of 0.69 [0.55-0.87] (p<0.001), 0.65 [0.40-1.06] (p=0.09), and 0.62 [0.46-0.84] (p<0.001) for TAT durations of 3, 6, and 12 months, respectively. No difference was seen in the occurrence of MACE, MI, stroke, or stent thrombosis between DAT and TAT across all 3 durations of TAT therapy. This is the largest pooled analysis comparing TAT to DAT stratified by duration of antithrombotic therapy. Our results revealed that DAT was associated with reduced bleeding risk despite no difference in other outcomes.