BackgroundBipolar voltage amplitude is capable of helping determine the ideal lesion size index (LSI) setting during radiofrequency (RF) ablation for atrial fibrillation (AF). ObjectiveTo determine whether voltage-guided pulmonary vein isolation (PVI) is noninferior to conventional LSI-guided PVI in patients with nonvalvular AF. MethodsThis was a multicenter randomized trial conducted over a period of 12 months. The primary efficacy endpoints of the study were AF recurrence, atrial flutter, and/or atrial tachycardia, and the noninferiority margin was set at a hazard ratio of 1.4. The primary safety end point was a composite of procedure-related complications. ResultsA total of 370 patients underwent randomization; 189 and 181 were assigned to the voltage (underwent voltage-guided PVI) and control (underwent conventional LSI-guided PVI) groups, respectively. The primary efficacy endpoint occurred in 22 patients (12.0%) in the voltage group and 23 (12.9%) in the control group (1-year Kaplan–Meier event-free rate estimates, 88.0% and 87.1%, respectively; hazard ratio, 1.00; 95% confidence interval [CI], 0.80 1.25). The primary safety endpoints were 4.8% in the voltage group and 6.6% in the control group (p = 0.2791). PVI time was significantly shorter in the voltage group (35.7 ± 14.5 min vs. 39.7 ± 14.7 min, p < 0.001). ConclusionVoltage-guided PVI was noninferior to conventional LSI-guided PVI with respect to efficacy in the treatment of patients with AF and its use significantly reduced procedure time.