While radiation therapy has been known to cause myocardial and pericardial damage, its role in accentuating coronary artery disease in the absence of traditional cardiovascular risk factors has been controversial. As younger patients with treatable cancers are being treated with mediastinal radiation, coronary artery disease as a cause for severe chest pain should be entertained as a possible diagnosis. We describe a 25-year-old male who presented with an inferior wall myocardial infarction 6 years after receiving mediastinal radiation and chemotherapy for Hodgkin's disease. He was subsequently treated by directional atherectomy to a 95% lesion in the right coronary artery. Histological examination of the atherectomy specimen revealed evidence of radiation-induced endothelial damage that had resulted in plaque formation and subsequent ischemia. Possible mechanisms for radiation-induced coronary artery disease and treatment options are discussed.