Aprotinin has been successfully used to reduce blood loss and blood product requirements in patients undergoing primary and reoperative cardiac operations. Its safety and efficacy during profound hypothermia and circulatory arrest have been questioned, however. A retrospective review compared 24 patients who received aprotinin during complex aortic procedures under profound hypothermia and circulatory arrest with 24 age-matched patients undergoing similar procedures without aprotinin. Activated clotting time was maintained at longer than 500 seconds (kaolin activating agent) or longer than 750 seconds (celite). We observed no statistically significant difference in the incidence of neurologic events (p not significant) or myocardial infarctions (p not significant), and there was a trend toward reduced in-hospital mortality rate in aprotinin-treated patients. A higher incidence of postoperative renal dysfunction was encountered in aprotinin-treated patients. Aprotinin recipients had a significant reduction in requirements for postoperative homologous erythrocytes (p = 0.01). We conclude that aprotinin may be safely and effectively used in patients undergoing deep hypothermia and circulatory arrest.