Objective: Optimal antithrombotic therapy following left atrial appendage closure (LAAC) with the Watchman occluder (Boston Scientific) remains uncertain. This study aimed to investigate the efficacy and safety of a 3-month dual antiplatelet therapy (DAPT) after LAAC. Methods: This was a post hoc analysis of a prospective study of patients who underwent successful LAAC with Watchman devices at the REGIOMED Hospitals of Coburg and Lichtenfels (Germany). Those treated from 11/2016 to 05/2018 received DAPT for 3 months (DAPT group); those from 02/2012 to 04/2017 received 45-day anticoagulant+aspirin followed by 4.5-month DAPT (ACT group). The primary efficacy outcome and safety outcome were analyzed. The net clinical benefit and bleeding events 1 year after treatment, and their independent risk factors were also explored. Results: There were 220 and 304 patients in the DAPT and ACT groups. The primary efficacy outcome were 9.5% vs. 6.3% [hazard ratio (HR), 1.58; 95% confidence interval (CI), 0.84-2.97; P=0.14]; the primary safety outcome were 4.5% vs. 5.9% (HR, 0.80; 95% CI, 0.38-1.69; P=0.57); the net clinical benefit were 13.6% vs. 11.8% (HR, 1.23; 95% CI, 0.75-2.02; P=0.39) over 1 year in DAPT and ACT groups, respectively. Age ≥75 years (HR, 2.08; 95%CI, 1.13-3.84; P=0.02) was identified as an independent predictor for the net clinical benefit. ACT (HR, 1.97; 95%CI, 1.12-3.50; P=0.02) was independently associated with bleeding events after procedure. Conclusions: In patients who underwent LAAC using the Watchman occluder, 3-month DAPT is associated with fewer bleeding events compared with ACT regimen.