SUMMARYAprotinin is a potent pharmacological agent which reduces bleeding and limits blood transfusion in current surgical practice. Many studies have been conducted in orthopedic surgery. Several trials have been performed in total hip replacement and total knee replacement patients, and aprotinin only moderately decreased blood loss requirements in these patients. Conversely, when aprotinin was used in patients with a high bleeding risk (cancer, sepsis, redo surgery, etc.), it developed a potent hemostatic activity and significantly decreased transfusion requirements. No increase in deep vein thrombosis and pulmonary embolism was observed. The only major side effect could be the potential occurrence of an anaphylactoid reaction. Prophylactic administration of aprotinin should be considered in extensive spine surgery and in high‐risk major orthopedic operations. The decision to use aprotinin will be guided by a risk/benefit analysis.