Aprotinin, a naturally occurring serine protease inhibitor, has found widespread application during cardiac surgical procedures as a consequence of its ability to decrease blood loss and transfusion requirements. While its efficacy in a variety of clinical situations associated with increased risk of blood loss has been well established, at the same time, various complications including anaphylaxis, renal insufficiency, graft closure and arterial thromboses have been reported in association with aprotinin administration. In order to more fully evaluate the risks and benefits associated with aprotinin usage, this review first of all examines the hazards associated with transfusion of blood and blood products. Consideration is then given to various alternatives to allogeneic transfusion, including autologous predonation, acute normovolemic hemodilution, perioperative cell salvage and intraoperative plasma sequestration. A critique of other available pharmacological therapies, specifically desmopressin, aminocaproic acid and tranexamic acid, reviewing their modes of action, efficacy and associated complications, is then made. The role of aprotinin in cardiac surgery is then discussed and its pharmacology, including consideration of its antifibrinolytic, platelet preserving and anti-inflammatory effects is reviewed. Finally, an analysis of potential complications associated with aprotinin administration is undertaken. Issues involving its influence on specific measures of anticoagulation, namely partial thromboplastin time and activated clotting time, and issues relating to graft patency, hypothermic circulatory arrest, renal function, and allergic reactions are analysed and interpreted. In summary, this review concludes that most of the risks associated with aprotinin administration primarily involve inadequate anticoagulation and those of developing an allergic reaction, particularly upon aproptinin re-exposure. The benefits of aproptinin to decrease blood loss and transfusion requirements are confirmed, and there is evidence pointing to the intriguing possibility of a potential salutary effect on perioperative central nervous system complications.