Orthotopic liver transplantation (OLT) can be associated with excessive blood loss. As a result, there may be increased risk of adverse outcomes. Activated recombinant factor VII (rFVIIa) has demonstrated the ability to improve hemostasis in a variety of disorders; however, there has been a limited amount of research into its use in OLT. The purpose of this dose-finding study was to examine the efficacy and safety of rFVIIa in the reduction of bleeding in patients undergoing OLT. In this doubleblind trial, patients with end-stage liver disease scheduled for OLT were randomized to 1 of 4 parallel study groups. They received a single intravenous bolus of rFVIIa (20, 40, or 80 g/kg) or placebo prior to surgery. The primary assessment endpoint was the total number of red blood cell (RBC) units transfused perioperatively. Safety was evaluated by adverse events reported. Eighty-three comparable patients were randomized to receive study product, with 82 ultimately undergoing OLT. There were no significant differences in required RBC units between the placebo and rFVIIa study groups. The number of adverse events was comparable between study groups. In conclusion, rFVIIa has a good safety profile in patients undergoing OLT. However, the doses studied did not have any effect on the number of RBC transfusions required. (Liver Transpl 2005;11:895-900.) O rthotopic liver transplantation (OLT) is associ- ated with excessive blood loss that requires transfusions, resulting in increased postoperative mortality, 1-4 longer stays in the intensive care unit, 1 increased infection rates, and reduced graft survival. [3][4][5][6] Clinical strategies to reduce blood loss include the use of blood products to correct preexisting coagulopathy (fresh frozen plasma, platelets, cryoprecipitate) or antifibrinolytic agents to correct fibrinolysis that may occur during the procedure. 7,8 The primary concerns with antifibrinolytic therapy are determining the appropriate dosage and addressing the potential risk of serious thromboembolic events. [8][9][10][11][12] Activated recombinant factor VII (rFVIIa; Novo-Abbreviations: OLT, orthotopic liver transplantation; rFVIIa, activated recombinant factor VII; RBC, red blood cell; AE, adverse event.