Aims Cardiac resynchronization therapy (CRT) is currently considered an important breakthrough in the treatment of selected patients with refractory heart failure. However, long-term predictors of mortality, morbidity and time to recovery of ventricular function for those patients who respond positively to CRT remain poorly investigated. Methods This is a retrospective follow-up study involving one hospital. Between August 2004 and October 2008, 211 consecutive patients with refractory heart failure received a CRT device in the Cardiology Division of Ospedale Civile Maggiore in Verona. The clinical characteristics studied were age, sex, heart rhythm, left ventricular end-systolic volume/body surface area (LVESV/BSA), left ventricular ejection fraction, QRS duration, type of bundle-branch block, cause, New York Heart Association functional class, pharmacological therapy and lead position. The objective of this study was to evaluate the effect of several baseline characteristics on long-term prognosis in heart failure patients treated with CRT. Results Non ischemic cause, left bundle-branch block and a basal LVESV/BSA <= 106 ml/m(2) or less were the only independent predictors of a positive response to CRT (P<0.005). Additionally, a reduction in LVESV/BSA after CRT was associated both with increased survival and reduced rehospitalization for heart failure (P<0.005). Conclusion A better selection of patients on the basis of cause, type of bundle-branch block and basal LVESV/BSA can increase the number of patients that would benefit from CRT.