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Background: Left atrial appendage closure (LAAC) is an alternative therapy for patients with nonvalvular atrial fibrillation who are not eligible for long-term oral anticoagulation. However, the optimal therapy after this procedure still is controversial, especially in a subgroup of patients with severe renal dysfunction., Objective: The purpose of this study was to evaluate the use of low-dose direct oral anticoagulation (l-DOAC) vs dual antiplatelet therapy (DAPT) after LAAC in patients with nonvalvular atrial fibrillation., Methods: We systematically searched PubMed, Embase and Cochrane. Outcomes were the incidence of device-related thrombus (DRT), major bleeding, stroke, cardiovascular mortality, all-cause mortality, thromboembolic events (DRT, ischemic stroke, transient ischemic attack, peripheral thromboembolism), and the composite outcome of thromboembolic events and major bleeding. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random effects model. Review Manager 5.4.1 was used for statistical analyses. Heterogeneity was assessed with I2 statistics., Results: A total of 1015 participants from 2 randomized controlled trials and 3 nonrandomized cohorts were included. The incidence of DRT was significantly reduced with l-DOAC relative to DAPT (0.81% vs 5.08%, respectively; RR 0.37; 95% CI 0.15-0.94; P = .04; I 2 = 0%). We also found the patients who used l-DOAC had a reduction in the composite outcomes of thromboembolic events and major bleeding (1.41% vs 11.13%; RR 0.14; 95% CI 0.05-0.36; P <.0001; I 2 = 0%)., Conclusion: In this systematic review and meta-analysis, the use of l-DOACs in patients with nonvalvular atrial fibrillation who underwent LAAC reduces the occurrence of the DRT and composite outcomes of thromboembolic events and major bleeding., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)