BACKGROUND Aprotinin has been used increasingly to reduce postoperative blood loss in open heart operations. Although it was reported as safe in earlier studies, the overall safety of prophylactic use has been questioned recently. Because of the potential for complications and the high cost, it will be reasonable to use aprotinin more selectively in the postoperative period. METHODS We prospectively studied the effect of postoperative low-dose aprotinin (2 million kallikrein inactivator units [280 mg]) on blood loss and transfusion requirements in patients undergoing cardiopulmonary bypass. Seventy-five patients were randomly assigned to three groups: prophylactic high-dose aprotinin (group 1), postoperative aprotinin (group 2), or a nonmedicated control group (group 3). RESULTS The three groups were comparable in all demographic and operative variables. Postoperative chest tube drainage was significantly decreased in both aprotinin groups compared with that in the control group (295 mL in group 1 and 325 mL in group 2 versus 411 mL in group 3; p < 0.05). No significant difference was seen between the two aprotinin groups. The use of homologous blood products was significantly less in group 1 and group 2 than in group 3 (1.15 +/- 1.13 U and 1.35 +/- 1.30 U versus 2.55 +/- 1.09 U; p < 0.05). CONCLUSIONS Our results suggest that postoperative aprotinin reduces blood loss and transfusion requirements comparably with prophylactic high-dose aprotinin. Thus, one can restrict its use to patients with excessive postoperative bleeding.