BackgroundPatients with nonvalvular atrial fibrillation (AF) not suitable for long‐term anticoagulant therapy undergo percutaneous left atrial appendage closure (LAAC) using the WATCHMAN device. The safety and efficacy of WATCHMAN‐FLX (WM‐FLX) compared with WATCHMAN‐2.5 (WM‐2.5), particularly in Asian populations, is unknown.MethodsWe evaluated the background, procedure, and clinical outcomes of 199 patients who underwent LAAC between September 2019 and December 2022 and compared WM‐2.5 (72 patients) with WM‐FLX (127 patients).ResultsThe mean age was 76 years, with 128 men, and 100 had nonparoxysmal AF (non‐PAF). The mean CHA2DS2‐VASc, and HAS‐BLED were 5.1, and 3.2 points, respectively. WM‐FLX group demonstrated a shorter procedure time than WM‐2.5 group (50 vs. 42 min, p = 0.001). The WM‐FLX group demonstrated no procedural‐related acute cardiac tamponade, which was significantly low (5.6% vs. 0%, p = 0.02), and a significantly higher rate of complete seal at 45‐day (63% vs. 80%, p = 0.04). WM‐FLX group had a significantly higher cumulative 1‐year incidence of device‐related thrombosis (DRT) than WM‐2.5 group (3.4% vs. 7.0%, Log‐rank p = 0.01). Univariate analysis identified two DRT risk factors in the WM‐FLX group: non‐PAF (odds ratio [OR] 7.72; 95% confidence interval [CI] 1.20–48.7; p = 0.04), and 35‐mm device (OR 5.13; 95% CI 1.31–19.8; p = 0.02).ConclusionsWM‐FLX significantly improved the procedural quality and safety of LAAC. However, DRT remains an important issue even in the novel LAAC device, being a hazard for patients with high DRT risk, such as having non‐PAF and using 35‐mm devices.