BACKGROUND: Left atrial appendage (LAA) patency after catheter ablation and LAA closure (LAAC) is a key determinant of postprocedure stroke. The effect of LAA electrical isolation (LAAEI) on LAA patency after LAAC in patients with atrial fibrillation (AF) remains unknown. Our objective was to explore the effect of LAAEI on LAA patency after catheter ablation and LAAC in patients with AF. METHODS: Patients with persistent AF who underwent combined catheter ablation and LAAC were enrolled. LAA patency was detected by cardiac computed tomographic angiography at 3 months after the procedure. RESULTS: A total of 686 patients with persistent AF with 3-month device surveillance by cardiac computed tomographic angiography were included initially. Propensity score matching analysis was conducted on the basis of clinical features, echocardiographic parameters and procedural characteristics, and 469 patients were matched, including 363 with non-LAAEI and 106 with LAAEI. Patients in matched groups showed 53.7% complete closure (no patency). Of the 46.3% of cases with LAA patency, visible peridevice leak was seen in 72.8%, and 27.2% had patency without visible peridevice leak. Compared with the non-LAAEI group, the LAAEI group had a lower rate of LAA patency (49.6% versus 34.9%; adjusted odds ratio, 0.69 [95% CI, 0.48-0.98]; P=0.040). LAAEI was protective against LAA patency with an odds ratio of 0.68, and the other predictor of contrast leak into the LAA was maximum diameter of LAA orifice (odds ratio, 1.04 [95% CI, 1.00-1.08]; P=0.046). CONCLUSIONS: LAAEI is an effective strategy for reducing LAA patency in patients with persistent AF undergoing combined catheter ablation and LAAC. REGISTRATION: URL: clinicaltrials.gov; Unique Identifier: NCT03788941.