The clinical outcome and the incidence of ischemic strokes in patients with hypertrophic cardiomyopathy (HCM) with and without atrial fibrillation (AF) were examined. Eighty-three patients with HCM, complicated by AF in 19 patients, and 131 patients with AF but without HCM were studied retrospectively. Primary endpoints (ischemic strokes or cardiac death, whichever occurred first) and ischemic strokes were examined by Kaplan-Meier curves. In the patients with HCM, the primary endpoints occurred more frequently in those with AF than in those without AF (event rate at 5 year 23.0% vs 12.3%, p < 0.01). Similarly, the frequency of ischemic strokes in HCM was also much higher with AF than without AF (23.0% vs 5.9% at 5 years, p < 0.01). According to multivariate Cox analysis, the strong independent risk factor for ischemic strokes in HCM was AF (p < 0.01), whereas in patients with AF they were HCM (p < 0.01) and age (p < 0.01). These results suggest that incidence of ischemic strokes in HCM is markedly increased if complicated by AF as compared with that in patients with AF alone.