We tested the efficacy and safety of aprotinin in 169 patients undergoing isolated reoperative myocardial revascularization. Patients were randomly assigned to high-dose aprotinin, low-dose aprotinin, or placebo treatment groups in a double-blind, placebo-controlled study. Treatment groups did not differ significantly with respect to age, sex, red cell mass, number of grafts, use of internal thoracic artery, or incidence of preoperative aspirin therapy. Patients treated with aprotinin had a significant reduction in postoperative chest tube drainage (720 +/- 753, 866 +/- 1,636, and 1,121 +/- 683 mL, respectively, for high-dose aprotinin, low-dose aprotinin, and placebo; p < 0.001). Transfusion requirements were reduced in aprotinin-treated patients (2.1 +/- 4.2, 4.8 +/- 11.8, and 4.1 +/- 6.2 units for high-dose, low-dose, and placebo, respectively; p < 0.001). A similar reduction in chest tube drainage and transfusion requirements was seen in patients using aspirin preoperatively. Q-wave myocardial infarctions were increased in the aprotinin subgroups (17.5%, 14.3%, and 8.9% for high-dose, low-dose, and placebo groups; not significant). Acute vein graft thrombosis was found in six of 12 vein grafts studied at postmortem examination in patients receiving aprotinin but not in any of five grafts in patients receiving placebo. We conclude that aprotinin is extremely effective in reducing bleeding and transfusion requirements and may increase the risk of graft thrombosis.