Cardiac resynchronization therapy (CRT) is an effective treatment for a large subgroup of chronic heart failure patients. Various attempts to improve the high non-responder rate of 30 % by preoperative asynchrony assessment have failed. We hypothesized that superior response to CRT is correlated with greater acute reduction of asynchrony and that a concordant left ventricular (LV) lead is beneficial compared to a discordant lead. Hundred and eight consecutive CRT patients from our center were prospectively included. Clinical status and asynchrony parameters were assessed before, 1 day and 6 months after CRT implantation. Super-response was defined as an increase of the LV ejection fraction by ≥15 % and a decrease in LV end systolic volume (LVESV) by ≥30 %. When the criteria for super-response were not met, average response was given with a decrease of baseline LVESV ≥15 %. Sixty eight patients were classified as responders (63 %). Comparing super- (n = 19) and average (n = 49) responders, we found that greater acute reduction of LV asynchrony (change of asynchronous segments under CRT: −1.3 vs. −0.4, p < 0.05; decrease of LV intraventricular delay: −34 ms vs. −16 ms, p < 0.05) is associated with superior reverse remodeling after 6 months. Importantly, asynchrony parameters of super-, average and non-responders were almost identical at baseline. A concordant LV lead (n = 63) was not associated with improved LV reverse remodeling compared to a discordant lead (n = 28): LVEF: +8.6 % vs. +7.8 %, p = 0.91; LVESV: −30.5 ml vs. −23.8 mL, p = 0.84. A greater immediate reduction of LV asynchrony predicts superior response. Preoperative asynchrony parameters do not correlate with outcome. A concordant LV lead is not superior to a discordant lead.