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Aims Little is known about the optimal right ventricular (RV) pacing site in cardiac resynchronization therapy (CRT). This study compares bi-ventricular pacing at the left ventricular (LV) free wall combined with two different RV stimulation sites: RV outflow tract (RVOT+LV) vs. RV-apex (RVA+LV). Methods and results Thirty-three patients (32 males) with chronic heart failure, NYHA class III-IV, optimal drug therapy, QRS-duration ≥150 ms, and chronic atrial fibrillation (AF) received CRT with two different RV leads, in the apex (RVA) or outflow tract (RVOT), together with an LV lead, all connected to a bi-ventricular pacemaker. Randomization to pacing in RVOT+LV or RVA+LV was made 1 month after implantation and cross-over to the alternate pacing configuration occurred after 3 months. The median age of patients was 69 ± 10 years, the mean QRS was 179 ± 23 ms, and 58% of patients had ischaemic heart disease. Seven patients had pacemaker rhythm at inclusion and 60% were treated with atrioventricular-junctional ablation before randomization. In the RVA+LV and RVOT+LV pacing modes, 67 and 63% (nonsignificant) responded symptomatically with a decrease of at least 10 points in the Minnesota Living with Heart Failure score. The secondary end-points (6-min walk test, peak oxygen uptake, N-Terminal fragment of B-type Natriuretic Peptide, and left ventricular ejection fraction) showed significant improvement between baseline and CRT, but not between RVOT+LV and RVA+LV. Conclusion In this randomized controlled study, the exact RV pacing site, either apex or outflow tract, did not influence the benefits of CRT in a group of patients with chronic heart failure and AF. ClinicalTrials.gov ID: NCT00457834.