ABSTRACT Background The efficacy and safety of tailored pulmonary vein isolation (PVI) guided by either left atrial wall thickness (LAWT) or bipolar voltage remain unclear. Objective The aim of this prospective study was to evaluate the efficacy and safety of each ablation strategy. Methods We conducted a prospective analysis of 97 patients with non‐valvular atrial fibrillation (AF) who underwent an initial RF catheter ablation procedure known as an extensive encircling PVI. Fifty patients underwent PVI using a wall thickness (WT)‐guided approach using ADAS 3D software and 47 patients using a voltage‐guided approach. In each strategy, high‐power short‐duration (HPSD) ablation was applied to regions with increased LAWT or elevated bipolar voltage, respectively, while very high‐power short‐duration (vHPSD) ablation was delivered to the remaining regions. Results The first‐pass PVI rate tended to be higher in the WT‐guided group compared to the Voltage‐guided group (43 [86%] vs. 34 [72%], p = 0.09), and the incidence of acute PV reconnection (APVR) tended to be lower (5 [10%] vs. 11 [23%], p = 0.07). The proportion of patients with PV gaps (defined as the combined occurrence of first‐pass failure and/or APVR) was significantly lower in the WT‐guided group (10 [20%] vs. 18 [38%], p = 0.04). The multivariable‐adjusted analysis demonstrated that WT‐guided ablation was significantly more effective than Voltage‐guided ablation in preventing PV gaps. Both ablation strategies were performed without any procedural complications. Conclusions WT‐guided ablation was associated with a significantly lower incidence of PV gaps than a conventional bipolar voltage‐guided strategy.