The efficacy of biventricular (BiV) pacing in patients with a narrow or moderately prolonged QRS duration remains questionable. To assess the hypothesis that electrical dyssynchrony is required to obtain hemodynamic benefit from BiV pacing by investigating the relationship between intrinsic QRS duration and hemodynamic response to BiV pacing in a patient population covering a broad spectrum of QRS duration. Eighty-two consecutive heart failure patients underwent cardiac resynchronization therapy implantation irrespective of their QRS duration. Thirty-four patients had a narrow QRS duration (<120 ms), whereas 11 patients had a moderately prolonged QRS duration (≥120 to <150 ms) and 37 patients had a severely prolonged QRS duration (≥150 ms). After implantation, invasive left ventricular (LV) dP/dt measurements were compared between intrinsic rhythm and simultaneous BiV pacing with an optimized atrioventricular delay. A high correlation (r = .65; P < .001) was observed between baseline QRS duration and changes in LV dP/dt(max) induced by BiV pacing. BiV pacing was ineffective in patients with a narrow QRS duration (+0.4% ± 6.1%; P = ns). No significant increase in LV dP/dt(max) was observed in patients with a QRS duration of ≥120 to <150 ms (+4.4% ± 6.9%; P = .06), whereas patients with a QRS duration of ≥150 ms exhibited a significant increase in LV dP/dt(max) (+17.1% ± 13.4%; P <.001). Only 9% of the patients with a narrow QRS duration exhibited a ≥10% increase in LV dP/dt(max). Baseline QRS duration is linearly related to acute hemodynamic response to BiV pacing. Patients with a narrow QRS duration do not derive hemodynamic improvement. This improvement is also limited in patients with a moderately prolonged QRS duration, raising questions about the potential clinical benefit of this therapy in these patients.