Objectives: The aim of this study was to compare-in patients with persistent and permanent atrial fibrillation(AF)-the efficacy and safety of left atrial ablation with that of a biatrial approach. Background: Left atrium-based catheter ablation of AF, although very effective in the paroxysmal form of the arrhythmia, has an insufficient efficacy in patients with persistent and permanent AF. Methods: Eighty highly symptomatic patients(age, 58.6±8.9 years) with persistent(n=43) and permanent AF(n=37), refractory to antiarrhythmic drugs, were randomized to two different ablation approaches guided by electroanatomical mapping. A procedure including circumferential pulmonary vein, mitral isthmus, and cavotricuspid isthmus ablation was performed in 41 cases(left atrial ablation group). In the remaining 39 patients(biatrial ablation group), the aforementioned approach was integrated by the following lesions in the right atrium: intercaval posterior line, intercaval septal line, and electrical disconnection of the superior vena cava. Results: During follow-up(mean duration 14±5 months), AF recurred in 39%of patients in the left atrial ablation group and in 15%of patients in the biatrial ablation group(p=0.022). Multivariable Cox regression analysis showed that ablation technique was an independent predictor of AF recurrence during follow-up. Conclusions: In patients with persistent and permanent AF, circumferential pulmonary vein ablation, combined with linear lesions in the right atrium, is feasible, safe, and has a significantly higher success rate than left atrial and cavotricuspid ablation alone. Objectives: The aim of this study was to compare-in patients with persistent and permanent atrial fibrillation (AF) -the efficacy and safety of left atrial ablation with that of a biatrial approach. Background: Left atrium-based catheter ablation of AF, very effective in the paroxysmal form of the arrhythmia, has an insufficient efficacy in patients with persistent and permanent AF. Methods: Eighty highly symptomatic patients (age, 58.6 ± 8.9 years) with persistent (n = 43) and permanent AF ), refractory to antiarrhythmic drugs, were randomized to two different ablation approaches guided by electroanatomical mapping. A procedure including circumferential pulmonary vein, mitral isthmus, and cavotricuspid isthmus ablation was performed in 41 cases (left atrial ablation group). In the remaining 39 patients the biatrial ablation group was integrated by the following lesions in the right atrium: intercaval posterior line, intercaval septal line, and electrical Results: During follow-up (mean duration 14 ± 5 ​​months), AF recurred in 39% of patients in the left atrial ablation group and in 15% of patients in the biatrial ablation group (p = 0.022 Multivariable Cox regression analysis showed that ablation technique was an independent predictor of AF recurrence during follow-up. Conclusions: In patients with persistent and permanent AF, circumferential pulmonary vein ablation, combined with linear lesions in the right atrium, is feasible, safe , and has a significantly higher success rate than left atrial and cavotricuspid ablation alone.