Background and Purpose—Association of mitral valve prolapse (MVP) with ischemic neurological events (INEs) is uncertain.Methods—In the community of Olmsted County (Minn), we identified all MVP diagnosed (1989 to 1998) in patients in sinus rhythm with no prior history of INE. We measured INE rates and compared them with expected rates in our community to define the excess risk of INE.Results—Among 777 eligible subjects (age, 49±20 years; 66% female; follow-up, 5.5±3.0 years), 30 patients had at least 1 INE during follow-up (at 10 years, 7±1%). Compared with expected INEs in the same community, subjects with MVP showed excess risk of lifetime INE (relative risk [RR], 2.2; 95% CI, 1.5 to 3.2;P<0.001) and during follow-up under purely medical management (RR, 1.8; 95% CI, 1.1 to 2.8;P=0.009). Independent determinants of INE were older age (RR, 1.08 per year; 95% CI, 1.04 to 1.11;P<0.001), mitral thickening (RR, 3.2; 95% CI, 1.4 to 7.4;P=0.008), atrial fibrillation (AFib) during follow-up (RR, 4.3; 95% CI, 1.9 to 10.0;P<0.001), and need for cardiac surgery (RR, 2.5; 95% CI, 1.1 to 5.8;P=0.03). INE 10-year rates were low in patients <50 years of age (0.4±0.4%,P=0.60 versus expected) but were excessive in patients >50 years of age (16±3%,P<0.001 versus expected) or with thickened leaflets (7±2%,P<0.001 versus expected). Predictors of follow-up AFib were age, mitral regurgitation, and left atrium diameter (allP<0.01).Conclusions—In the community, subjects with MVP display a lifetime excess rate of INE compared with expected. Clinical (older age) and echocardiographic (leaflets thickening) characteristics define patients with MVP at high risk for INE, and subsequent AFib or need for cardiac surgery, both related to the degree of mitral regurgitation, increase the risk of INE.