AIMS: To identify the predictive value of a presumed optimal left ventricular lead positions (LV-Ps) on the long-term clinical outcome in patients with cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Clinical information was collected from patient files in consecutive patients treated with CRT from 1997 to 2007. A presumed optimal LV-Ps were defined as a position between 2 and 5 o'clock in the short-axis circumference and basal or mid-ventricular in the long axis. Symptomatic response was defined as improvement in NYHA class (>or=1) and echocardiographic response as improvement in left ventricular ejection fraction of >or=5% absolute. We included 567 patients [median age 66 years, 453 (80%) male]. The LV-Ps were optimal in 334 (59%) patients. The hazard ratio for all-cause mortality with an optimal LV-Ps was unadjusted 0.79 (0.59-1.06) and adjusted 0.99 (0.71-1.40). The odds ratio (OR) for symptomatic response with an optimal LV-Ps was unadjusted 1.13 (0.79-1.64) and adjusted 1.05 (0.67-1.64), and the OR for echocardiographic response was unadjusted 1.60 (1.02-2.49) and adjusted 1.42 (0.88-2.31). CONCLUSION: A presumed optimal LV-Ps between 2 and 5 o'clock in the short-axis circumference and basal or mid-ventricular in the long axis is not associated with a lower mortality or a better clinical response in patients treated with CRT.