Two recent studies have shown decreased blood loss in patients given aprotinin undergoing primary hip replacement surgery. Because patients undergoing bilateral (bTHA) or revision total hip arthroplasty (rTHA) suffer more blood loss than those undergoing primary THA, we studied consecutive patients undergoing bTHA or rTHA who were randomized to receive either a blinded solution of 3.8 x 10(6) Kallikrein inactivation units (KIU) aprotinin (n = 29) or placebo (n = 24) throughout the surgical procedure. Total blood loss, measured as intraoperative suction losses, weight of sponges, and postoperative volumetric drainage, was compared between groups. Aprotinin patients had significantly less total blood loss 1498 +/- 110 mL (mean +/- SEM) versus 2096 +/- 223 (P = 0.022), and transfused patients in the aprotinin group received fewer packed red blood cells than placebo-treated patients (confidence interval for the difference -1.69, -0.07). In addition, assessment of biochemical markers of hepatic and renal function did not disclose any clinically important differences between groups. Patients were also assessed for development of deep venous thrombosis (DVT) by preoperative and predischarge bilateral lower limb compression ultrasound. None of the aprotinin-treated patients and three placebo-treated patients demonstrated DVT. Unless this trend for decreased DVT with aprotinin can be confirmed, it is questionable whether the slight reduction in blood loss justifies routine use of this expensive drug.