High-dose aprotinin was used in 20 patients undergoing primary or repeat operations on the thoracic or thoracoabdominal aorta using cardiopulmonary bypass and hypothermic circulatory arrest. The activated clotting times immediately before the establishment of hypothermic circulatory arrest exceeded 700 seconds in all but 1 patient. Three patients (15%) required reoperation for bleeding. Seven patients died during hospitalization, and 5 had postmortem examination. Platelet-fibrin thrombi were present in multiple organs including the coronary arteries of 4 patients with myocardial infarction or failure, the pulmonary arteries of 2 patients, 1 of whom died of acute right ventricular failure, the brains of 2 patients who sustained a stroke, and the kidneys of 4 patients, 3 of whom had development of renal dysfunction. Renal dysfunction occurred in 13 patients (65%), and all were 65 years of age or older. Five of these patients required hemodialysis. Among 20 age-matched patients who had similar operations without aprotinin, there was one hospital death (5%) from myocardial infarction, and renal dysfunction developed in 1 patient (5%), who did not require dialysis. None of these 20 patients required reoperation for bleeding. Although aprotinin has been shown to reduce blood loss in patients having cardiac operations employing cardiopulmonary bypass, this benefit was not attained in this group of patients with thoracic aortic disease in whom hypothermic circulatory arrest was used. Use of aprotinin in elderly patients undergoing these procedures was associated with an increased risk of renal dysfunction and failure, and of myocardial infarction and death.