Background. - The prognostic value of secondary mitral regurgitation (MR) at baseline versus immediately after and several months after cardiac resynchronization therapy (CRT), beyond left ventricular (LV) reverse remodelling, has yet to be investigated. Aim. - To evaluate the clinical significance of secondary MR before and at two timepoints after CRT in a large cohort of consecutive patients with heart failure (HF) and reduced LV ejection fraction. Methods. - A total of 198 patients were recruited prospectively into a registry, and underwent echocardiography at baseline and immediately after CRT (on the day of hospital discharge). Echocardiography was also performed 9 months after CRT in 172 patients. The impact of significant secondary MR (>= moderate) on all-cause death, cardiovascular death and hospitalization for HF was studied at each stage. Results. - The frequency of significant secondary MR decreased from 23% (n = 45) to 8% (n = 16) immediately after CRT. Among the 172 patients who underwent echocardiography 9 months after CRT, 17 (10%) had significant secondary MR. During a median follow-up of 48 months, 49 patients died and 36 were hospitalized for HF. Patients with significant secondary MR immediately after or 9 months after CRT had an increased risk of all-cause death, cardiovascular death and hospitalization for HF during follow-up (P < 0.05 for all endpoints). After adjustment for LV reverse remodelling, significant secondary MR 9 months after CRT remained associated with an increased risk of all-cause death (adjusted hazard ratio [HR] 3.77; P = 0.014), cardiovascular death (adjusted HR 5.36; P = 0.037), and hospitalization for HF (adjusted HR 7.33; P = 0.001). Conclusions. - Significant secondary MR despite CRT provides important prognostic information beyond LV reverse remodelling. Further studies are needed to evaluate the potential role of new percutaneous procedures for mitral valve repair in improving outcome in these very high-risk patients. (C) 2017 Elsevier Masson SAS. All rights reserved.