Background— Percutaneous left atrial appendage (LAA) closure is an emerging option for patients with atrial fibrillation at high risk for cerebrovascular events. The multicenter FLAAC registry (French Nationwide Observational LAA Closure Registry) was established to assess LAA closure outcomes in everyday practice. Methods and Results— Four hundred thirty-six patients referred from April 2013 to September 2015 to 33 French interventional cardiology centers for percutaneous LAA closure were included prospectively in the FLAAC registry. Mean age was 75.4±0.4 years. The stroke risk was high (mean CHA ₂ DS ₂ –VASc score, 4.5±0.1) and most patients had experienced clinically significant bleeding (HAS-BLED score, 3.1±0.05). The device used was Amplatzer LAA occluder in 58% and the Watchman device in 42% of the patients. The procedural success rate was 98.4%. Median postprocedure follow-up was 12.0 (11.8–12.0) months and a single patient was lost to follow-up. During the periprocedural and subsequent follow-up period, procedure-related severe adverse events occurred in 21 (4.9%) and 10 (2.3%) patients, respectively. One-year cumulative incidences of ischemic stroke and cerebral hemorrhage were 2.9% (1.6–5.0) and 1.5% (0.7–3.2), respectively. Overall, 1-year mortality was 9.3% (6.9–12.5) with 7 of the 39 deaths related or possibly related to the device or procedure. Conclusions— This nationwide prospective registry shows that, in the French population, LAA closure is mainly used in patients with high comorbidity rates and a poor prognosis. LAA closure in such patients seems reasonable to decrease the stroke rate. The overall health status of these patients should be taken into account during the preprocedural evaluation process. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT02252861.