The CLOSURE-AF trial compared percutaneous left atrial appendage closure (LAAC) with medical therapy in patients with atrial fibrillation at high risk of stroke and bleeding.[1] Patients were randomized in a 1:1 ratio with a median follow-up of 3 years.[1] The primary endpoint was the first occurrence of ischemic or hemorrhagic stroke, systemic embolism, cardiovascular or unexplained death, or major bleeding (BARC ≥3).[1] LAAC failed to demonstrate non-inferiority to medical therapy for this composite outcome.[1] Event guidelines favored medical therapy.[1] Cardiovascular or unexplained death was 9.47 vs. 7.45 events per 100 patient-years (HR 1.25), overall mortality 14.83 vs. 13.49 (HR 1.12).[1] Safety events in the LAAC group included cardiac tamponade 1.12%, device embolization 0.22%, major bleeding requiring transfusion 4.04%, and procedural death 0.44%.[1]