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Left atrial appendage closure (LAAC) reduces the risk of thromboembolic stroke in atrial fibrillation. Peri-device leak (PDL) after LAAC may affect the subsequent risk of thromboembolism. We conducted a systematic review and meta-analysis to evaluate the effect of PDL after LAAC. We searched PubMed/Medline, Embase, and Google Scholar for studies reporting outcomes of PDL after LAAC from inception through October 2022. The primary outcome was the composite of stroke, transient ischemic attack (TIA), or systemic embolism (SE). Secondary outcomes included all-cause and cardiovascular mortality, ischemic stroke, TIA, and device-related thrombus. Outcomes were pooled using random-effects models. We used I 2 statistics to assess statistical heterogeneity; I 2 >50% considered significant heterogeneity. This study included 54,279 patients from 11 studies (6 observational, 2 nonrandomized controlled trials [non-RCTs] primary results, 2 RCT post hoc analyses, and 1 analysis combining 2 RCTs data). PDL was associated with a significant increase in the composite outcome of stroke, TIA, or SE (odds ratio 1.63, 95% confidence interval 1.06 to 2.52, p = 0.03, I 2  = 43%) as compared with cases with no PDL. There were no significant differences in all-cause or cardiovascular mortality, ischemic stroke, TIA, or device-related thrombus. In conclusion, PDL after LAAC is associated with an increased risk of thromboembolism (composite stroke, TIA, or SE) without impacting mortality., Competing Interests: Declaration of Competing Interest Dr Goldsweig is a consultant at Inari Medical and receives speaking fees from Philips, Edwards. The remaining authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)