Optimization of left ventricular pacing site or interventricular pacing delay improves the efficacy of biventricular pacing (BiVP). Cardiac output (CO) based optimization, however, is invasive and slow. QRS duration (QRSd) is noninvasive and responds rapidly. Accordingly, we investigated the utility of QRSd for BiVP optimization in a model of acute right ventricular (RV) pressure overload. In seven anesthetized open-chest pigs, BiVP was implemented with right atrial and RV pacing wires. A 6-electrode array was placed behind the LV. Heart block was established by alcohol ablation. The pulmonary artery was snared to double peak RV pressure. Fifty-four combinations of left ventricular pacing site and interventricular pacing delay were tested in random order over 30-second intervals. QRSd was assessed from electrocardiogram lead II, CO from aortic flow probe, and ventricular function from micromanometers. Comparisons were made with the Pearson's correlation coefficient (r). QRSd narrowing was associated with improved RV function and transseptal synchrony, but correlation with CO was poor. Additionally, QRSd averaged over the last 20 cardiac cycles in each interval was compared with values averaged over successive cardiac cycles following each reprogramming. Seven cardiac cycles after reprogramming, the average r-value went above 0.90 and plateaued. QRSd-based optimization merits further study during BiVP in patients with congestive heart failure.