Aprotinin, a naturally occurring protease inhibitor derived from bovine lung, is used prophylactically to minimize the amount of perioperative blood loss in patients undergoing coronary artery bypass graft surgery who are at high risk for excessive bleeding. A retrospective multicenter evaluation of aprotinin use was performed in high-risk coronary artery bypass graft patients treated either with aprotinin or according to usual-care to assess (1) differences in demographic and medical history characteristics, and (2) clinical and economic outcomes associated with their care. This study suggests that in many cases, the cost of aprotinin is offset by reductions in overall cost. Additional study is required to better understand this potential. In other cases, however, a more conservative approach to aprotinin use appears to be warranted.