BACKGROUND: Biventricular (BiV) stimulation is the preferred means of delivering cardiac resynchronization therapy (CRT), although left ventricular (LV)-only stimulation might be as safe and effective. B-LEFT HF is a prospective, multicenter, randomized, double-blind study aimed to examine whether LV-only is noninferior to BiV pacing regarding clinical and echocardiographic responses. METHODS: B-LEFT HF randomly assigned 176 CRT-D recipients, in New York Heart Association class III or IV, with an LV ejection fraction or =130 milliseconds, to a BiV (n = 90) versus LV (n = 86) stimulation group. Clinical status and echocardiograms were analyzed at baseline and 6 months after CRT-D implant to test the noninferiority of LV-only compared with BiV stimulation. RESULTS: The proportion of responders was in line with current literature on CRT, with improvement in heart failure composite score in 76.2% and 74.7% of patients in BiV and LV groups, respectively. Comparing LV versus BiV pacing, the small differences in response rates and corresponding 95% CI indicated that LV pacing was noninferior to BiV pacing for a series of response criteria (combination of improvement in New York Heart Association and reverse remodeling, improvement in heart failure composite score, reduction in LV end-systolic volume of at least 10%), both at intention-to-treat and at per-protocol analysis. CONCLUSIONS: Left ventricular-only pacing is noninferior to BiV pacing in a 6-month follow-up with regard to clinical and echocardiographic responses. Left ventricular pacing may be considered as a clinical alternative option to BiV pacing.