Bleeding after cardiopulmonary bypass remains a cause for concern, requiring reexploration of the chest in approximately 3 percent of patients who have had operations on the heart. We examined the possibility that this problem might be alleviated by desmopressin acetate (DDAVP), which increases the plasma level of von Willebrand factor and improves hemostasis in mild hemophilia and other conditions associated with defective platelet function. In a double-blind, prospective, randomized trial, we studied the effect of intraoperative desmopressin acetate in 70 patients undergoing various cardiac operations requiring cardiopulmonary bypass. Patients undergoing uncomplicated primary coronary-artery bypass grafting were not included. The drug significantly reduced mean operative and early postoperative blood loss (1317 +/- 486 ml in the treated group vs. 2210 +/- 1415 ml in the placebo group); of the 14 patients whose 24-hour blood loss exceeded 2000 ml, 11 had received the placebo. Plasma levels of von Willebrand factor were higher after desmopressin acetate than after placebo. Patients with the most bleeding had relatively low levels of von Willebrand factor before operation, suggesting a role for this factor in the hemorrhagic tendency induced by extracorporeal circulation. There were no untoward side effects of desmopressin acetate. We conclude that the administration of desmopressin acetate can be recommended to reduce blood loss in patients undergoing complex cardiac operations. The beneficial effect of the drug on hemostasis after cardiopulmonary bypass may be related to its effect on von Willebrand factor.