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Aims: Cardiac Resynchronization Therapy (CRT) is associated with a particularly high non-response rate in patients with atrial fibrillation (AF). We aimed to assess the effectiveness of triple-site (Tri-V) pacing CRT in this population., Methods and Results: Prospective observational study of patients with permanent AF who underwent CRT implantation with an additional right ventricle lead in the outflow tract septal wall. After implantation, programming mode (Tri-V or biventricular pacing) was selected based on cardiac output determination. Patients were classified as responders if NYHA class was reduced by at least one level and echocardiographic ejection fraction (EF) increased ≥ 10%, and as super-responders if in NYHA class I and EF ≥ 50%. Forty patients (93% male, mean age 72 ± 10 years) were included. Thirty-three were programmed in Tri-V. The following results pertain to this subgroup. At baseline, 58% were in NYHA class III and 36% NYHA class II. At 1 year follow-up, Minnesota QoL score was reduced (36 ± 23 vs. 8 ± 6; P = 0.001) and the 6MWT distance improved (384 ± 120 m to 462 ± 87 m, P = 0.003). Mean EF increased (26% ± 8 vs. 39 ± 10; P < 0.001 at 6 months and 41 ± 10; P < 0.001 at 12 months). Responder rate was 59% at 6 months and 79% at 12 months. Super-responder rate was 9% at 6 months and 16% at 12 months. One year survival free from heart failure hospitalization was 87.9%., Conclusion: Tri-V CRT yielded higher response and super-response rates than usually reported for CRT in patients with permanent AF using clinical and remodeling criteria.