Patients with hypertrophic cardiomyopathy (HC) die suddenly. Proposed risk factors for sudden cardiac death (SCD) in HC are youth, a family history of SCD, syncope, and ventricular tachycardia. Hemodynamic variables have not convincingly proved to be risk factors for SCD. Therefore, this study was designed to examine predictors of SCD in a large number of patients with HC during long-term follow-up periods. The relation of studied variables (clinical, electrocardiographic, echocardiographic, hemodynamic, and exercise test findings) to SCD in 309 patients with HC who were initially diagnosed during 1971 through 1994 (mean follow-up 9.4 years) was examined by multivariate analysis. SCD occurred in 28 patients. Independent predictors of SCD were a smaller difference between peak and rest systolic blood pressure during exercise testing (p=0.006), and higher left ventricular outflow tract pressure gradient at rest (p=0.003). Exercise-related SCD occurred in 8 patients and exercise-unrelated SCD in 20 patients (mean age 28 vs 47 years, p <0.05). Thus, patients of exercise-related SCD were younger and had smaller increases in systolic blood pressure during exercise testing, whereas patients with exercise-unrelated SCD were older and had higher left ventricular outflow tract pressure gradient.