Background: Cardiac resynchronization therapy (CRT) benefits patients with advanced heart failure. The role of atrioventricular nodal (AVN) ablation in improving CRT outcomes, including survival benefit in CRT recipients with atrial fibrillation, is uncertain. Objective: The purpose of this study was to assess the impact of AVN ablation on clinical and survival outcomes in a large atrial fibrillation and heart failure population that met the current indication for CRT and to determine whether AVN ablation is an independent predictor of survival in CRT recipients. Methods: Of 154 patients with atrial fibrillation who received CRT-D, 45 (29%) underwent AVN ablation (+AVN-ABL group), whereas 109 (71%) received drug therapy for rate control during CRT (-AVN-ABL group). New York Heart Association (NYHA) class, electrocardiogram, and echocardiogram were assessed before and after CRT. Survival data were obtained from the national death and location database (Accurint). Results: CRT comparably improved left ventricular ejection fraction (8.1% ± 10.7% vs 6.8% ± 9.6%, P = .49) and left ventricular end-diastolic diameter (-2.1 ± 5.9 mm vs -2.1 ± 6.7 mm, P = .74) in both +AVN-ABL and -AVN-ABL groups. Improvement in NYHA class was significantly greater in the +AVN-ABL group than in -AVN-ABL group (-0.7 ± 0.8 vs -0.4 ± 0.8, P = .04). Survival estimates at 2 years were 96.0% (95% confidence interval [CI] 88.6%100%) for +AVN-ABL group and 76.5% (95% CI 68.1%85.8%) forAVN-ABL group (P = .008). AVN ablation was independently associated with survival benefit from death (hazard ratio [HR] 0.13, 95% CI 0.030.58, P = .007) and from combined death, heart transplant, and left ventricular assist device (HR 0.19, 95% CI 0.060.62, P = .006) after CRT. Conclusion: Among patients with atrial fibrillation and heart failure receiving CRT, AVN ablation for definitive biventricular pacing provides greater improvement in NYHA class and survival benefit. Larger-scale randomized trials are needed to assess the clinical and survival outcomes of this therapy. © 2010 Heart Rhythm Society.