The effect of pharmacological dose of α-tocopherol on heart health was determined in Wistar rats. Animals were randomly assigned to either C (control, n = 11) or E (α-tocopherol, n = 11) group. Animals received corn oil (C) or α-tocopherol dissolved in corn oil (250 mg α-tocopherol/[kg body wt/day]) (E) by gavage for a 7-week period. Rats underwent echocardiogram and were analyzed for cardiomyocyte histology and cardiac α-tocopherol absorption at the end of the study period. As compared to the C group, α-tocopherol-supplemented group showed significantly (p < 0.05) lower body weight (E, 412.8 g vs C, 480.3 g) and total cardiac weight (E, 0.94 g vs C, 1.08 g); cardiomyocyte histological impairment; smaller left ventricle (LV) (LV end-diastolic diameter (E, 7.22 mm vs C, 7.37 mm), lower LV systolic [left ventricle fractional shortening (E, 47.6% vs C, 53.6%) and ejection fraction ratio (E, 85.4 vs C, 89.9)] and diastolic [early peak velocities of diastolic transmitral flow (E, 64.6 cm/sec vs C, 75.1 cm/sec)] function. The α-tocopherol uptake in target tissue was confirmed by determination of α-tocopherol concentration medians in cardiac tissue (E, 109.91 nmol/kg vs C, 52.09 nmol/kg). The current study indicates that pharmacological dose of α-tocopherol supplementation can induce cardiotoxicity in healthy rats.