Background Extensive ablation strategies are currently performed in addition to pulmonary vein isolation (PVI) to improve the clinical outcome of patients with drug-refractory persistent atrial fibrillation (AF). Ablation of complex fractionated atrial electrograms (CFAEs), linear lesions, and/or isolation of the left atrial appendage (LAA) are thought to improve arrhythmia-free survival. Objective The purpose of this study was to assess the durability of wide-area left atrial appendage isolation (LAAI) achieved by PVI, an anterior line, and a mitral isthmus line. Methods Seventy-one patients with intentional or incidental LAAI during repeat catheter ablation for treatment of persistent AF were included. The initial ablation strategy was PVI. Additional ablation strategies were performed only if PVI failed to maintain stable sinus rhythm. Durability of LAAI was assessed during a subsequent ablation procedure for arrhythmia recurrences (n = 23) or a subsequent percutaneous LAA closure (n = 48). Results LAAI was performed after a mean of 3 ± 1 procedures. Ablation strategies included circumferential PVI in 71 patients (100%), mitral isthmus line in 64 (90%), anterior line in 60 (85%), CFAE in 27 (38%), and roof line in 13 (18%). LAAI occurred after ablation and bidirectional block of LA linear lesions in 63 patients (89%) and during extensive CFAE ablation in 8 patients (11%). After a median of 105 [61;426] days, the LAA remained electrically isolated in 52 of 71 patients (73%). Conclusion Wide-area LAAI after extensive catheter ablation for persistent AF is durable in the majority of patients. The potential clinical benefit of LAAI for maintaining stable sinus rhythm requires further investigation.