BACKGROUND: Modification of the low-voltage zone in the left atrium (LA-LVZ) in addition to pulmonary vein isolation (PVI) has not shown sufficient improvement in arrhythmia-free survival in patients with persistent atrial fibrillation (PerAF). Further, the effect of electrical posterior wall isolation (PWI) is controversial. We investigated the impact of existence of LA-LVZ on the outcome of patients undergoing additional PWI for PerAF. METHODS: A total of 347 patients with PerAF who underwent primary catheter ablation with LA-LVZ based strategy were retrospectively analyzed. Voltage mapping in the left atrium (LA) was performed during sinus rhythm. Additional LVZ ablation was performed in patients with LA-LVZ. The operators decided whether additional PWIs were to be performed. RESULTS: Of 347 patients, 108 had LA-LVZ. In the LVZ group, patients with additional PWI (N = 70) had higher rates of freedom from tachyarrhythmia recurrence than those without (77.1% vs. 42.1%, p < 0.001). Furthermore, even when patients were limited to those with LA-LVZ in areas other than the posterior wall (N = 85), PWI had higher success rates (80.9% vs. 42.1%, p < 0.001). In contrast, in patients without LVZ (N = 239), there was no significant difference in the rate of successful outcome between those with and without PWI (81.3% vs. 88.1%, p = 0.112). On the other hand, the patients with PWI had greater atrial tachycardia (AT) recurrence rate than those without PWI (10.0% vs. 2.5%, p = 0.003). CONCLUSIONS: PWI, in addition to PVI and LVZ modification, may improve single procedural outcomes in patients with PerAF who have LVZ, regardless of the distribution in the LA. A combination of voltage-guided ablation and PWI may be a simple, tailored, and effective ablation strategy.