Abstract Funding Acknowledgements Type of funding sources: None. Introduction / Background Left atrial appendage occlusion (LAAO) has emerged as a nonpharmacological alternative for stroke prevention in patients with atrial fibrillation (AF). Contemporary data regarding the characteristics and outcomes of patients undergoing this procedure compared to a control group not treated with LAAO are limited. Purpose Our objective was to compare outcomes following first LAAO implantation in an exhaustive nationwide matched cohort. Methods This French longitudinal cohort study was based on the national hospitalization database covering hospital care from for the entire population. All adults (age ≥18 years) hospitalized in French hospitals with AF from January 1, 2015 to January 1, 2020, who underwent a LAAO implantation were identified. Owing to the non-randomized nature of the study, and considering for significant differences in baseline characteristics between AF patients treated with LAAO and no LAAO, propensity-score matching was used to control for potential confounders of the treatment outcome relationship. The primary outcome was a composite of ischemic stroke, major bleeding (Bleeding Academic Research Consortium ≥3) or all-cause mortality during follow-up. Results After propensity score matching 2,682 patients with LAAO were matched 1:1 with 2,682 AF patients not treated with LAAO. Baseline characteristics of matched patients are illustrated in Figure 1. Mean follow-up was 7 months (median 5, interquartile 1-11 months). As illustrated in Figure 2, AF patients treated with LAAO had a significantly lower risk of the primary composite outcome as compared with patients not treated with LAAO (hazard ratio [HR] 0.59, 95% confidence interval [CI]: 0.52 to 0.68). Total events and event rates per 100 patient-years were (LAAO vs. no LAAO) 315 vs. 591 and 20.6%/year vs. 36.1%/year, respectively. The risk of ischemic stroke was comparable between groups (HR 1.06, 95% CI: 0.75 to 1.17), while risk of major bleeding (HR 0.49, 95% CI: 0.37 to 0.65) and all-cause mortality (HR 0.57, 95% CI: 0.48 to 0.67) were significantly lower in patients treated with LAAO. Conclusion Among AF patients with a high risk of bleeding, our nationwide study highlighted a high risk of clinical events during follow-up. Patients treated with LAAO may have similar stroke prevention efficacy but lower risk of major bleeding and mortality when compared to propensity score-matched patients not treated with LAAO.