Cryopreserved valved homograft has become the conduit of choice for right ventricular outflow tract reconstruction in pediatric cardiac surgery. Aortic homografts have been frequently used in pulmonary position, but accelerated aortic homograft fibrocalcification may occur. Blood group incompatibility between receiver and homograft donor may play a central role in this context.Between 1993 and 2000, 59 children (mean age 6.4 +/- 4.4 years) received cryopreserved valved homografts for right ventricular outflow tract reconstruction and were followed from 2 to 10 years clinically, with echocardiography and chest radiography for detection of development of homograft calcifications. Seventeen patients were 3 years or younger. Fifty aortic (85%) and 9 pulmonary homografts were all used in pulmonary position. Thirty-three patients (56%) had the same blood group (ABO) as the homograft donor (iso group), and 26 were blood group-incompatible (non-iso group).No deaths occurred during follow-up. Six patients (10.2%) required homograft replacement because of severe fibrocalcifications, and another 3 showed moderate homograft calcifications (5.1%) at last examination. Freedom from moderate to severe homograft calcification at 8 years (Kaplan-Meier) was 95.2% for the iso group and 72.9% for the non-iso group (P <.0001). Homograft calcifications occurred within 2 years of implantation in 6/9 patients (67%) in the non-iso group.Blood group incompatibility between receiver and homograft donor seems to play an important role in the development of accelerated fibrocalcifications in cryopreserved homografts, particularly in the very young (3 years old or younger). Blood group compatibility should therefore be respected to avoid accelerated homograft fibrocalcifications.