To assess the rate and predictors of complications in patients with mitral valve prolapse (MVP), 316 subjects (mean age 42 +/- 15 years) with echocardiographic MVP were followed prospectively for a mean of 102 months: 220 (70%) were women, 225 (71%) had clinically recognized MVP, and 91 (29%) were detected in family studies. During follow-up, 11 patients (0.4/100 subject-years) required mitral valve surgery, 6 died of cardiac causes (0.2/100 subject-years), 7 developed cerebral ischemia (0.3/100 subject-years), and 2 developed active infective endocarditis (0.1/100 subject-years). The overall rate of fatal and nonfatal complications (1/100 patient-years) was higher in men than in women (odds ratio [OR] 3.2, p < 0.003), in subjects aged > 45 than < or = 45 years (OR 3.4, p = 0.002), in clinically recognized patients than in affected family members (OR 3.8, p < 0.02), and in those with a holosystolic murmur (OR 26.9, p < 0.00005); the overall rate was lower in those with a midsystolic click (OR 0.3, p < 0.002). Echocardiographic left ventricular or atrial diameter > or = 6.0 or > or = 4.0 cm, respectively, was associated with a 16.7- and 15.1-fold higher likelihood, respectively, of subsequent complications.(ABSTRACT TRUNCATED AT 250 WORDS)