Midterm outcomes for patients presenting with heart failure and functional mitral regurgitation (MR) treated with Mitraclip remain unclear. Pubmed, Medline, and Google Scholar were systematically searched for studies enrolling patients with severe-moderate MR who underwent Mitraclip implantation. All events after at least 6 months were the primary safety end point (including death, rehospitalization for heart failure, and reinterventions), whereas change in the ejection fraction, left ventricular volumes, arterial pulmonary pressure, and left atrial diameters were considered as secondary end points. Meta-regression analysis was performed to evaluate the effect of baseline clinical and echocardiographic parameters on efficacy outcomes: 875 patients were included in 9 studies; 1.48 clips (1.3 to 1.7) for patients were implanted, and after a median follow-up of 9 months (6 to 12), 409 patients (78% [75% to 83%]) were in class New York Heart Association I/II and 57 (11% [8% to 14%]) still had moderate-to-severe MR. Overall adverse events occurred in 137 (26% [20% to 31%]) of the patients and 78 (15% [1% to 17%]) of them died; 6-minute walk test improved by 100 m (83 to 111), whereas a significant reduction in left ventricular volumes and systolic pulmonary pressure was reported. At meta-regression analysis, an increase in left ventricle systolic volumes positively affected reduction of volumes after Mitraclip, whereas atrial fibrillation reduced the positive effect of the valve implantation on ejection fraction on end-diastolic and -systolic volumes. In conclusion, Mitraclip represents an efficacious strategy for patients with heart failure and severe MR. It offers a significant improvement in functional class and in cardiac remodeling, in patients with severely dilated hearts as well, although its efficacy remains limited in the presence of atrial fibrillation.