Background: Medical therapy of atrial fibrillation (AF) can be challenging in patients with Brugada electrocardiograms (ECGs). The purpose of this study was to investigate the efficacy of pulmonary vein (PV) isolation (PVI) in AF patients with Brugada ECGs. Methods and Results: PVI was performed in 6 consecutive patients exhibiting Brugada ECGs (type I in 1, type II in 4, and type III in 1) at baseline. In all patients exhibiting type II or III Brugada ECGs but 1, the administration of sodium-channel blockers converted those ECG patterns to a type I. Five of 6 (83%) patients were free of symptomatic AF without any antiarrhythmic drugs after the first procedure. In the 1 remaining patient with AF recurrence and newly developed atrial tachycardia (AT), the residual conduction gaps of the 3 previously isolated PVs and a focal AT originating from the mitral isthmus were eliminated in the 2nd session. Finally, during the follow-up period (11±6 months) after the last procedure, all patients were free of any symptomatic atrial arrhythmias without any antiarrhythmic drugs. No other complications occurred. Conclusions: Because of the concerns of proarrhythmias with antiarrhythmic drugs, PVI may be an effective strategy for highly symptomatic patients with AF who have a Brugada ECG pattern.