Aims Cardiac resynchronization therapy (CRT) is an effective treatment for refractory congestive heart failure (CHF). However, up to 30% of patients do not respond to CRT. The aim of this study was to identify clinical and electrocardiographic (ECG) predictors of a positive response to CRT. Methods and results This retrospective study included 139 consecutive patients successfully implanted with a CRT device (mean age, 68 +/- 9 years, 113 men). At baseline, 69% of patients were in New York Heart Association (NYHA) functional class III, and 31% in class IV, mean left ventricular ejection fraction was 21 + 6%, and mean QRS duration was 188 +/- 28 ms. In each patient, left and right ventricular leads were placed to attain the shortest QRS duration during biventricular stimulation. Patients were classified at 6 months as responders to CRT (n = 100) if they were alive, they had not been re-hospitalized for management of CHF, and the NYHA class had decreased by 1 point, and/or peak VO2 or 6 min hall-walk increased by > 10%. All others were classified as non-responders (n = 38; one patient was lost to follow-up). Uni- and multivariate logistic regression analyses were performed to detect a pre- or intra-operative predictor of a positive response to CRT. Among multiple demographic, clinical, and ECG variables, the amount of QRS shortening (AQRS) associated with biventricular stimulation was the only independent predictor of a positive (37 + 23 ms) vs. negative (11 +/- 23 ms) response to CRT (P < 0.001). Conclusion A positive response to CRT was observed in 73% of patients at 6 months and predicted only by AQRS.