The relationship among myocardial fibrosis, segmental strains, and hypertrophic cardiomyopathy (HCM) in patients with preserved left ventricular ejection fraction is not known. We evaluated this relationship in 39 consecutive patients with HCM with transthoracic echocardiography and delayed hyperenhancement magnetic resonance imaging 20 minutes after injection of 0.2 mmol/kg of gadolinium. Speckle tracking echocardiography was used to assess left ventricle strains. Fibrosis was determined semiautomatically with magnetic resonance imaging, using a 12-segment short-axis left ventricular model. Myocardial fibrosis was detected in 23 of 39 patients with HCM. The mean end-systolic longitudinal strain correlated with the number of fibrotic segments (r = 0.47, P =.002) and total myocardial fibrosis (r = 0.46, P =.003). Fibrosis and wall thickness were both multivariate predictors of lower segmental longitudinal strain (P <.003). Longitudinal, circumferential, and radial strains are decreased in patients with HCM even in the absence of fibrosis. Myocardial fibrosis is associated with depressed longitudinal strain in patients with HCM.