Background Cardiac allograft vasculopathy (CAV) is a major limitation to the long-term success of cardiac transplantation. Although there are published descriptions of the lesions, there have been no studies delineating the pathology of CAV in a large series of patients who underwent retransplantation for CAV. Methods We reviewed archival records and microscopic sections of surgically explanted hearts from 64 patients who underwent cardiac retransplantation: 54 adults (18 to 70 years old) and 10 children (3 to 15 years old). Vascular lesions were categorized as showing intimal fibromuscular hyperplasia, atherosclerosis and/or inflammation. The degree of luminal narrowing was estimated from gross descriptions and microscopic sections. Results In total, 75% of hearts had evidence of acute cellular rejection, mostly mild. Intramyocardial arteries showed primarily intimal fibromuscular hyperplasia and inflammation with no atheromas present. Large and branch epicardial coronary arteries were narrowed in at least one artery of all hearts. Lesions in the epicardial coronary arteries were composed of intimal fibromuscular hyperplasia, atherosclerosis and/or inflammation affecting one or more vascular layers (intima, media and adventitia). Severe CAV with >75% luminal narrowing was seen in the LAD in 17% of hearts, the LCx in 17% and the RCA in 22% of hearts. Two hearts had severe narrowing of the left main coronary artery. Nineteen arteries had luminal thrombi. All hearts had narrowing of smaller epicardial branch coronary arteries that was often severe. Atheromas were present in arteries of adults and children; thus, not all atheromas could be considered pre-existing prior to transplantation. Both arteries and veins showed intimal hyperplasia and inflammation. Conclusions CAV is a pathologically multifaceted disorder that affects large and small epicardial coronary arteries of adults and children, with different types of lesions: intimal fibromuscular hyperplasia; atherosclerosis; and/or inflammation (vasculitis). Therapies to address this disease must take into account the protean nature of the vascular lesions.