abstract Aprotinin is a potent pharmacological agent that reduces bleeding. In current surgical practices, the rate of blood transfusions has decreased with the use of aprotinin. Recently, studies using aprotinin have been conducted in orthopedic surgery. Several trials have been performed in patients undergoing total hip replacement and total knee replacement. Aprotinin moderately decreased blood loss in these patients. When aprotinin was used in patients with a high-risk of bleeding (ie, patients with cancer, sepsis, or undergoing reoperation), potent hemostatic activity occurred and the rate of blood transfusions significantly decreased. No increase in deep vein thrombosis and pulmonary embolism was observed. One adverse effect was the potential occurrence of an anaphylactoid reaction. Prophylactic administration of aprotinin should be considered in extensive spine surgery and in high-risk orthopedic operations. The decision to use aprotinin can be guided by a risk/benefit analysis.