Young children undergoing complex cardiac operation lose more blood after cardiopulmonary bypass than do older patients. This study was designed to investigate the effect of desmopressin on blood loss during the first 24 hours after cardiac operation in children undergoing principally complex surgical procedures. The study consisted of a randomized, blinded comparison of 112 pediatric patients who received either desmopressin 0.3 microgram/kg or saline solution placebo after cardiopulmonary bypass. A coagulation profile including bleeding time, quantitation of von Willebrand factor, and qualitative analysis of the factor VII:von Willebrand factor complex was performed before, 30 minutes after, and 3 hours after the operation. Blood loss and blood replacement were recorded for the first 24 hours after the operation. The surgeon classified the technical difficulty of each procedure as simple or complex. Statistical analysis was performed with Student's unpaired t test and chi 2 analysis. Significance was defined as p < 0.05. Results are listed as mean +/- standard deviation. Data collection was completed for 95 patients. The mean age of all patients was 26 +/- 40 months, and the mean weight was 10 +/- 11 kg, with 84% undergoing complex procedures. There were no differences between the desmopressin and placebo groups with respect to age, weight, or surgical complexity. Twenty-four-hour blood loss and replacement between the desmopressin and placebo groups were not different (blood loss: desmopressin 30 +/- 33 ml/kg, placebo 35 +/- 36; blood replacement: desmopressin 65 +/- 43 ml/kg, placebo 64 +/- 46 ml/kg). Coagulation profiles between the desmopressin and placebo groups were not different at any time. We conclude that desmopressin does not reduce blood loss or blood replacement in young children after cardiopulmonary bypass for either simple or complex cardiac surgical procedures.