The clinical significance of T-wave alternans (TWA) in hypertrophic cardiomyopathy (HCM) is unclear, so SV1+RV5 and QT dispersion on 12-lead electrocardiograms (ECG), the parameters of the left ventricle on echocardiography and the family history of HCM and sudden death were investigated in 53 patients with HCM who experienced TWA. The maximal numbers of successive ventricular ectopic beats (max VE) and nonsustained ventricular tachycardia (NSVT) were measured by Holter monitoring. In 13 patients, genetic abnormalities were examined. In 22 patients, the hypertrophy of myocytes, disarray and fibrosis were histopathologically examined using a scoring method. TWA was positive in 27 patients (TWA+ group), negative in 14 (TWA- group) and indeterminate in 12. The ECG and echocardiographic parameters, family history and genetic abnormalities did not significantly differ between the TWA+ and TWA- groups. Max VE, the percentage of patients with NSVT and disarray score in the TWA+ group were significantly higher than those in the TWA- group (3.6+/-3.6 vs 1.3+/-0.7, 37% vs 0%, 1.9+/-1.1 vs 0.7+/-0.5; p<0.05). TWA in HCM correlates with histopathological changes, especially disarray and ventricular tachyarrhythmia, and measuring it may be a noninvasive means of detecting high-risk patients with HCM.