Objectives: This study sought to compare 2 ways of achieving cardiac resynchronization. Background: Cardiac resynchronization therapy (CRT) in patients with symptomatic heart failure and left bundle branch block (LBBB) can be achieved with His-bundle pacing correcting the bundle branch block (His-CRT). The present study is the largest randomized study comparing His-CRT and biventricular pacing (BiV-CRT) to date. Methods: Fifty patients with symptomatic heart failure, left ventricular ejection fraction (LVEF) ≤35% and LBBB according to electrocardiography were randomized 1:1 to His-CRT or BiV-CRT and followed for 6 months. At implantation, 7 patients crossed over from His-pacing to LV-pacing in the His-CRT group and 1 patient crossed over from LV-pacing to His-pacing in the BiV-CRT group. Results: His-corrective pacing was achieved in 72% of the patients in the His-CRT group. Intention-to-treat 6-month follow-up LVEF increased by 16 ± 7% in the His-CRT group compared with 13 ± 6% in the BiV-CRT group (nonsignificant) and improvements were seen in clinical and physical parameters in both treatment arms with no significant differences between the groups. Pacing thresholds were higher for His-CRT compared with BiV-CRT both at implantation (1.8 ± 1.2 V vs. 1.2 ± 0.8 V; p < 0.01) and at 6-month follow-up (2.3 ± 1.4 V vs. 1.4 ± 0.5 V; p < 0.01). The per-protocol LVEF was significantly higher at 6 months (48 ± 8% vs. 42 ± 8%; p < 0.05) and the end-systolic volume was lower (65 ± 22 ml vs. 83 ± 27 ml; p < 0.05) in His-CRT patients compared with BiV-CRT. Conclusions: In heart failure patients with LBBB, His-CRT provided similar clinical and physical improvement compared with BiV-CRT at the expense of higher pacing thresholds.