Background: Aprotinin use in adults is increasing, and its use in children has recently been reported. Methods: The efficacy of aprotinin in children was tested in 80 children. Patients were in four groups: reoperations (59), neonates (8), extremely cyanotic children (6), and other complex repairs (7). The results were compared with those of 55 control infants and children: reoperations (25), neonates (10), cyanotic (10) and complex (10). Treatment groups were identical in age, sex ratio, cross-clamp time, and bypass time. Results: Patients treated with aprotinin had a significant reduction in chest tube drainage (16.5 ± 9.8 versus 33.4 ± 22.1 mL · kg-1 · h-1; p < 0.001) and time to skin closure (64.2 ± 23.7 versus 80.1 ± 24.6 minutes; p < 0.001). Transfusion requirements were decreased in aprotinin-treated patients (4.2 ± 3.4 versus 6.7 ± 5.2 donors; p < 0.001). All of the control patients were exposed to at least one donor, whereas 10/80 (12.5%) of the aprotinin-treated group had no blood use (p < 0.006). There were no cases of renal insufficiency or allergic reactions in children receiving aprotinin. Three patients had thrombotic episodes: 2 superior vena caval problems and a lower extremity deep venous thrombosis. There were 3 cases of mediastinitis in the aprotinin group versus none in control patients (p < 0.05). Conclusions: We conclude aprotinin is an effective means of reducing bleeding, operating time, and donor exposure in infants and children. An increased rate of thrombosis and possibly mediastinitis are potential problems.