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Purpose: The recommended stroke prevention for patients with atrial fibrillation (AF) and increased risk of ischemic stroke is oral anticoagulation (OAC). Parts of the patient population are not eligible due to contraindication, and percutaneous left atrial occlusion (LAAO) can then be a preventive treatment option. The aim of this systematic review and meta-analysis is to estimate the long-term clinical effectiveness of LAAO as stroke prevention in patients with AF, increased risk of ischemic stroke, and contraindication to OAC., Methods: We performed a systematic review and meta-analysis, using Poisson random effect models, to estimate the incidence rate (events per 100 patient-years) of ischemic stroke, transient ischemic attack, major bleeding, and all-cause death after LAAO treatment. We also calculated the risk reduction of ischemic stroke with LAAO compared with no stroke prevention estimated through a predicted risk in an untreated population (5.5 per 100 patient-years)., Results: We included 29 observational studies in our meta-analysis, including 7 951 individuals and 12 211 patient-years. The mean CHA 2 DS 2 -VASc score among the patients in the included studies is 4.32. The pooled incidence rate of ischemic stroke is 1.38 per 100 patient-years (95% CI 1.08; 1.77). According to a meta-regression model, the estimated incidence rate of ischemic stroke at CHA 2 DS 2 -VASc 4 is 1.39 per 100 patient-years. This implies a risk reduction of 74.7% with LAAO compared to predicated risk with no stroke prevention., Conclusions: Our results suggest that LAAO is effective as stroke prevention for patients with AF, increased risk of stroke, and contraindication to oral anticoagulation., (© 2021. The Author(s).)