To characterize plaque morphologic characteristics of transplant coronary artery disease early and late after cardiac transplantation, 72 patients were studied with intravascular ultrasonography during routine coronary angiography (group 1, 25 patients ≤2 months after surgery; group 2, 47 patients ≥12 months after surgery). Both groups had comparable baseline characteristics. Three hundred fifty-one segments were imaged in 127 coronary arteries (4.9 ± 1.8 segments per patient). By intravascular ultrasonography, relevant intimal thickening (>0.3 mm) was found in the majority of patients (68% for group 1 and 72% for group 2). Angiography detected abnormal findings in only 16% and 32% for groups 1 and 2, respectively. Mean intimal index was higher in patients late after transplantation (27% ± 12% vs 17% ± 12%, respectively; p < 0.01). Maximal and mean plaque thickness were comparable in both groups, whereas a higher mean plaque circumference was found in group2 (278 ± 66 degrees vs 211 ± 75 degrees, respectively; p < 0.002). The lesions were more eccentric in patients early after transplantation (mean eccentricity index 95% ± 7% vs 77% ± 15%, respectively; p < 0.0001). Diffuse, concentric intimal thickening was not a common pattern. Maximal plaque thickness correlated with donor age ( r = 0.50, p < 0.0001). Coronary lesions were frequent even early after transplantation, with predominantly eccentric plaque morphologic characteristics indicative of preexisting atherosclerosis. Later after transplantation, a more homogeneous plaque distribution was seen, partly with diffuse concentic intimal thickening. Late transplant coronary artery disease appears to be a combination of preexisting native and acquired immune-mediated coronary artery disease. (Am Heart J 1997;133:29-35.)