To assess the feasibility, short-term durability and clinical outcomes of MitraClip® therapy for mitral regurgitation (MR) in patients with end-stage heart failure and a severely reduced left ventricular (LV) ejection fraction. We analysed retrospectively collected data from seven European centres. Included in the study were 50 heart failure patients [mean age 70 ± 11 years, 38 men (76%)] with a LV ejection fraction ≤25% and MR of at least grade 3+. All patients had functional MR, were in New York Heart Association (NYHA) functional class III or IV, and their mean logistic EuroSCORE was 34%. The patients underwent a total of 53 MitraClip® procedures; one or more clips were implanted in 50 procedures (48 patients), for an acute procedural success rate of 94%. Severity of MR was reduced in all successfully treated patients, 44 (92%) were discharged with MR ≤2+. Thirty-day mortality was 6%; cumulative survival at 6 months was 81.2%. Clinical and echocardiographic 6-month follow-up data were obtained from 32 and 31 successfully treated patients, respectively. At 6 months, MR ≤2+ was present in 27 (87%) of 31 patients, and 23 (72%) of 32 patients were in NYHA functional class I or II. Six-minute walk distance improved significantly, and significant reductions in LV volumes indicative of reverse LV remodelling were concordant with significant reductions in N-terminal pro-brain natriuretic peptide plasma levels. MitraClip® therapy reduces functional MR in patients with end-stage heart failure and marked LV dysfunction and entails clinical benefit at 6 months.