BACKGROUND: The effect of electrical delay at the left ventricular (LV) pacing site on acute hemodynamic response with cardiac resynchronization therapy (CRT) has been investigated only in small observational studies. OBJECTIVES: This study evaluates the impact of electrical delay, as assessed by interventricular (right ventricular-LV]) interval, on the acute hemodynamic response to CRT in a large, diverse multicenter cohort. METHODS: A total of 144 patients in 3 prospective studies, the PATH-CHF (Pacing Therapies in Congestive Heart Failure) I and II and the CRTAVO (CRT Optimization Algorithm Validation Study), were pooled and analyzed. At the time of CRT implantation, all pacing leads, pressure catheters placed in the right ventricle and left ventricle, and the surface electrocardiogram were connected to an external pacing computer. A standardized, randomized stimulation protocol was used to assess response. RESULTS: The RV-LV interval was associated with an increase in the rate of LV pressure rise response. In the full cohort, LV effective contractility monotonically increased with a prolongation of the RV-LV time. Other significant predictors of the increase in rate of LV pressure rise were QRS duration and, to a lesser extent, female sex and ischemic etiology. CONCLUSIONS: RV-LV and QRS durations are strong predictors of the acute hemodynamic response with CRT. These findings may help in patient selection, lead placement, and pacing benefit expectation.