We tested the hypothesis that myocardial microvascular abnormalities occur and are influenced by clinical features in 30 patients with hypertrophic cardiomyopathy (HC) using intravenous myocardial contrast echocardiography. Patients with HC were subdivided into 3 groups: nonobstructive HC (n = 12), obstructive HC (n = 10), or HC with systolic dysfunction and heart failure (n = 8). In patients with nonobstructive HC and obstructive HC, subendocardial peak myocardial contrast intensity at the mid-septal area was significantly decreased and the transmyocardial difference of peak myocardial contrast intensity between subendocardial and periendocardial regions at the mid-septal area was significantly related to regional wall thickness. Reduced peak myocardial contrast intensities at the mid-septal subendocardial and periendocardial regions were observed in patients with HC and heart failure. Our study indicates that subendocardial microvascular abnormalities during end-systole may be associated with severity of regional myocardial hypertrophy in patients with nonobstructive HC and obstructive HC. In addition, progressive microvascular damage may occur in patients with HC and heart failure.