Mitral regurgitation due to bileaflet prolapse and ischemic causes can be difficult to repair. Midterm experience of the Alfieri edge-to-edge repair as an alternative to valve replacement is reported. Twenty-six patients with severe mitral regurgitation underwent the Alfieri repair between January 1998 and December 2000 (group 1); 15 cases were due to bileaflet prolapse and 7 were of ischemic origin. During the same period, valve replacement was performed in 36 patients (group 2), 20 of whom had similar indications. Follow-up was complete to a mean of 15 months (range, 1-28 months). There was no early death in either group. During follow-up, there was no reoperation in group 1, while 2 patients in group 2 required reoperations due to prosthetic valve endocarditis. There were 4 major thromboembolic or bleeding events in group 2, and none in group 1. All patients in group 1 had trivial to mild mitral regurgitation on follow-up echocardiography. The mean mitral valve gradient was significantly higher in group 2 compared to group 1 (7.2 versus 3.2 mm Hg, p = 0.001). The edge-to-edge repair is associated with good early and midterm results. Long-term follow-up is required to evaluate the durability of this technique.