Our objective was to improve hemodynamics by synchronous right and left site ventricular pacing in patients with severe congestive heart failure (CHF). Previous studies reported a benefit of dual chamber pacing with a short AV delay in patients with severe CHF. Other works, however, show contradictory results. Deleterious effects due to a desynchronization of right (RV) and left ventricular (LV) contractions have been suggested. This study included eight subjects with widened QRS and end-stage heart failure despite maximal medical therapy, who refused, or were not eligible to undergo heart transplantation, Each patient underwent a baseline, invasive hemodynamic evaluation with insertion of three temporary leads to allow different pacing configurations, including RV apex and outflow tract pacing, and biventricular pacing between the RV outflow tract and LV and RV apex and LV. According to the results of this baseline study, the configuration of preexistent pacemakers was modified or new systems were implanted to allow biventricular pacing, which, in patients with sinus rhythm, was atrial triggered. Biventricular pacing increased the mean cardiac index (CI) by 25% (from a baseline of 1.83 +/- 0.30 L/min per m2, P < 0.006), decreased the mean V wave by 26% (from a baseline of 36 +/- 12 mmHg, P < 0.004), and decreased pulmonary capillary wedge pressure by 17% (from a baseline of 31 +/- 10 mmHg, P < 0.01). Four patients died (1 preoperatively, 1 intraoperatively, 2 within 3 months, and 1 of a noncardiac cause). The four surviving patients have clinically improved from New York Heart Association Functional Class IV to Class II. In these survivors, CI decreased by 15% (P < 0.007) when multisite pacing was turned off during follow-up. In patients with end-stage heart failure, multisite pacing may be associated with a rapid and sustained hemodynamic improvement.