Background: The present study was designed to evaluate the respective value of left ventricular (LV) reverse remodeling (changes in LV end-systolic volume relative to baseline (Delta LVESV)) or LV performance improvement (Delta LV ejection fraction (Delta LVEF) or Delta Global longitudinal strain (GLS)) to predict long-termoutcome in a prospective cohort of consecutive patients receiving routine cardiac resynchronization therapy (CRT). Methods: One hundred and seventy heart failure patients (NYHA classes II-IV, LVEF <= 35%, QRS width >= 120 ms) underwent echocardiography before and 9 months after CRT. The relationships between Delta LVESV, Delta LVEF, Delta GLS and outcome (all-cause mortality and/or CHF hospitalization, overall mortality, cardiovascular mortality, CHF hospitalization) were investigated. Results: During a median follow-up of 32 months, 20 patients died and 27 were hospitalized for heart failure. Delta LVESV, Delta LVEF or Delta GLS were significantly associated with all-cause mortality or CHF hospitalization (adjusted hazard's ratio (HR) per standard deviation 0.58 (0.43-0.77), 0.39 (0.27-0.57) or 0.55 (0.37-0.83) respectively, all p < 0.01) and all other endpoints (all p < 0.01). Patients with Delta LVESV >= 15%, Delta LVEF >= 10% and Delta GLS >= 1% had a reduced risk of mortality or CHF hospitalization (adjusted HR = 0.25 (0.12-0.51), p < 0.001, adjusted HR = 0.26 (0.13-0.54), p < 0.001 and adjusted HR0.38 (0.19-0.75), p=0.006 respectively). Overall performance of multivariate models was better using Delta LVESV or Delta LVEF compared with Delta GLS. Interobserver agreement was excellent for Delta LVESV (Intraclass correlation coefficient -ICC-0.91) and Delta GLS (ICC 0.90) but modest for.LVEF (ICC 0.76) in a sample of 20 patients from the study population. Conclusions: LV reverse remodeling assessed by Delta LVESV is a strong and reproducible predictor of outcome following CRT. Compared with Delta LVESV, Delta LVEF and Delta GLS have important shortcomings: poorer reproducibility or lower predictive value. (C) 2015 Elsevier Ireland Ltd. All rights reserved.