The optimal ablation technique for persistent and long-standing persistent atrial fibrillation (AF) is unclear. Both linear lesion (LL) and ganglionated plexus (GP) ablation have been used in addition to pulmonary vein isolation (PVI), but no direct comparison of the 2 methods exists. The aim of this study is to assess the comparative safety and efficacy of 2 different ablation strategies-PVI+LL vs PVI+GP ablation -in patients with persistent or long-standing persistent AF. Two hundred sixty-four consecutive patients with persistent/long-standing persistent AF were randomly assigned to 2 different ablation schemes: PVI+LL (n = 132) and PVI+GP (n = 132) ablation. Consistent sinus rhythm (SR) off antiarrhythmic drug was assessed after follow-up of at least 3 years with the use of an implanted monitoring device. All procedural end points were acutely achieved. At 12 months after a single procedure, 47% of the patients treated with PVI+LL were in SR compared to 54% of the patients treated with PVI+GP (P = .29). At 3 years, 34% of the patients with PVI+LL and 49% of the patients with PVI+GP maintained SR (P = .035). Atrial flutter was more frequent in the PVI+LL group than in PVI+GP group (18% vs 6%; P = .002). After a second procedure in 78 patients of the PVI+LL group and 55 patients of the PVI+GP group, the long-term overall success rate was 52% and 68%, respectively (P = .006). PVI+GP ablation confers superior clinical results with less ablation-related left atrial flutter and reduced AF recurrence compared to PVI+LL ablation at 3 years of follow-up.