Aprotinin is a serine protease inhibitor with antithrombotic, antifibrinolytic, and antiinflammatory effects. It is effective in reducing bleeding and the need for blood transfusions after cardiac surgery with cardiopulmonary bypass. Additional benefits, such as cerebral protection, are hypothesized but not yet thoroughly substantiated. The safety of aprotinin has been questioned based on a phase IV analysis of large data sets, including patients undergoing cardiac surgery. Potential risks including increased occurrences of stroke, myocardial infarction, renal failure, and death are implied by these analyses; however, adequate study group matching is lacking from these nonrandomized, retrospective studies. In October 2007, a large randomized controlled trial comparing antifibrinolytics in patients undergoing cardiac surgery was stopped after a preliminary analysis suggested a trend toward an increase in all-cause 30-day mortality associated with aprotinin. Subsequently, the manufacturer of aprotinin temporarily suspended marketing and halted all shipment of aprotinin on a worldwide basis. Pending a complete analysis of this study, the use of aprotinin could be considered as one component of a blood conservation strategy. After contemplating the benefits and risks of this controversial drug, clinicians should reserve its use for patients at high risk for postoperative blood loss.