The aim of the study was to prospectively evaluate a cohort of patients with hypertrophic cardiomyopathy (HC) after coronary flow reserve (CFR) assessment of the left anterior descending coronary artery. Sixty-eight patients with HC (40 men, mean +/- SD 58 +/- 12 years of age) underwent dipyridamole (up to 0.84 mg/kg over 6 minutes) echocardiography with CFR evaluation of the left anterior descending coronary artery by Doppler. Seventy-four age- and gender-matched, apparently healthy subjects served as controls. A CFR value <2.0 was considered abnormal. CFR was decreased in patients with HC versus controls (2.12 +/- 0.39 vs 2.78 +/- 0.58, p <0.0001). CFR was abnormal in 26 of 39 symptomatic and in 5 of 29 asymptomatic patients with HC (67% vs 17%, p <0.0001). In addition, patients with HC with left ventricular obstruction had decreased CFR (p <0.0001) compared with those without obstruction. During follow-up (22 +/- 13 months), 27 events occurred: 1 sudden death, 1 nonfatal myocardial infarction, 4 cardioverter-defibrillator implantations, 6 hospitalizations for heart failure, 5 unstable anginas, 2 syncopes, and 8 atrial fibrillations. Three-year event rate was markedly higher in patients with abnormal than in those with normal CFR (79% vs 17%, p <0.0001). Events were more frequent in symptomatic than in asymptomatic patients (62% vs 10%, p <0.0001). However, the latter had a 10-fold increased risk of events in the presence of abnormal CFR (40% vs 4%, p = 0.02). In conclusion, mean CFR is markedly lower in patients with HC than in apparently healthy subjects. Abnormal CFR is a strong and independent predictor of outcome in patients with HC.