Myocardial ischemia and left ventricular dysfunction have been documented in young adults with familial hypercholesterolemia. We investigated whether speckle-tracking echocardiography can be used to detect subclinically impaired global and regional myocardial function in patients with this lipid disorder. This single-center study included 47 patients with familial hypercholesterolemia and 37 healthy control subjects who underwent transthoracic Doppler echocardiography and speckle-tracking echocardiography from January 2003 through December 2016. Conventional echocardiographic and strain parameters in the 2 groups were analyzed and compared. Left ventricular dimensions were significantly larger at end-diastole (P=0.02) and end-systole (P=0.013), left ventricular walls were significantly thicker (P <0.0001), and the early transmitral/early diastolic mitral annular velocity ratio was significantly higher (P=0.006) in the patient group than in the control group. In the patient group, global longitudinal and circumferential strain values were significantly lower (P <0.0001) and global radial strain values significantly higher (P=0.006); all segmental longitudinal strain (P <0.04) and most segmental circumferential strain values (P ≤0.01) were significantly lower; and some segmental radial strains, especially at the apex, were significantly higher (P ≤0.04). However, average longitudinal, circumferential, and radial strains in the different segments of the 3 main coronary artery territories were significantly lower in the patient group (P <0.01). Global longitudinal strain (r=0.561; P=0.001) and global circumferential strain (r=0.565; P <0.0001) were inversely correlated with low-density-lipoprotein cholesterol levels. We conclude that speckle-tracking echocardiography can be used to detect subclinical global and regional systolic abnormalities in patients with familial hypercholesterolemia.