The efficacy of cardiac resynchronization therapy (CRT) in patients with atrial fibrillation (AF) and the need for atrioventricular junction ablation in these patients is controversial. The aim of the study was to analyze CRT results in patients with permanent AF. A total of 470 consecutive patients who underwent CRT in 6 centers were included in this study. Of these patients, 126 (27%) had permanent AF. Patients were evaluated at baseline and 12 months. No difference was found in the magnitude of improvement experienced by patients with AF compared with those in sinus rhythm (SR) with respect to quality of life, distance in 6-minute walking test, and left ventricular reverse remodeling. Despite the beneficial effects of CRT, death from refractory heart failure at 12 months was higher in patients with AF (17 of 126; 13.5%) than those in SR (14/344; 4.1%; p <0,001). Furthermore, permanent AF was an independent predictive factor for mortality from refractory heart failure (hazard ratio 5.4, 95% confidence interval 1.9 to 15.1). In conclusion, patients with AF treated with CRT who survived at the 12-month follow-up had the same functional improvement and remodeling as those in SR. However, AF was an independent risk factor for mortality from heart failure after CRT implantation.