Evidence exists that the serine protease inhibitor, aprotinin, when used in high dosage, can reduce the bleeding associated with cardiopulmonary bypass. This high dosage is particularly effective in patients at increased risk for bleeding. Less convincing information is available for regimens that use a lower dose and its place in routine cardiac surgery has not been fully resolved. Some studies have shown significant benefit from a single dose added to the cardio-pulmonary bypass prime and we re-examined this alternative. In a randomized, prospective, double-blinded study, we compared this single dose method with placebo in a low risk adults undergoing a first procedure. Benefit was considered established if a significant reduction in blood loss or the use of transfused blood products was seen. We found a significant reduction in red cell transfusion but no improvement in blood loss or blood component transfusion in the treated group. This included patients maintained on aspirin as well as those not receiving aspirin. Aspirin significantly increased blood loss in both control and treatment groups and the usage of blood products in the treatment group. Aprotinin in this low, single dosage was not confirmed as an effective means of improving hemostasis following CPB in routine cardiac surgery.