To assess the very long-term clinical and echocardiographic results of the edge-to-edge repair for mitral regurgitation (MR) due to isolated prolapse or flail of the anterior leaflet.From 1991 to 2004, 139 patients (age, 54±14.4 years; left ventricular ejection fraction 56%±7.8%, New York Heart Association class I-II in 68.9%, atrial fibrillation in 20.1%) with severe degenerative MR due to isolated segmental prolapse or flail of the anterior leaflet were treated with the EE technique combined with annuloplasty. MR had resulted from prolapse or flail of the central scallop of the anterior leaflet (A2) in 105 patients (75.5%) and scallops A1 or A3 in 34 (24.4%).No hospital deaths occurred. At hospital discharge, MR was absent or mild in 130 patients (93.5%) and moderate (2+/4+) in 9 (6.4%). The clinical and echocardiographic follow-up data were 97.1% complete (mean length, 11.5±3.73 years; median, 11; longest duration, 21.5). At 17 years, the actuarial survival was 72.4%±7.89%, freedom from cardiac death was 90.8%±4.77%, and freedom from reoperation was 89.6%±2.74%. At the last echocardiographic examination, recurrence of MR grade≥3+ was documented in 17 patients (17 of 135, 12.5%). Freedom from MR grade≥3+ at 17 years was 80.2%±5.86%. At multivariate analysis, the predictors of MR recurrence grade≥3+ were residual MR greater than mild at hospital discharge (hazard ratio, 7.4; 95% confidence interval, 2.5-21.2; P=.0001) and the use of posterior pericardial rather than prosthetic ring annuloplasty, which was very close to statistical significance (hazard ratio, 2.8; 95% confidence interval, 0.9-8.7; P=.06).In patients with MR due to segmental anterior leaflet prolapse, the very long-term results of the edge-to-edge repair combined with annuloplasty were excellent.