Background: Orthotopic liver transplantation (OLT) is associated with a large amount of blood loss. This article examines the impact of the initiation of a transfusion-free program in January 2000 for Jehovah's Witnesses (JWs) on the overall use of blood products in non-JW patients undergoing OLT. Design: Retrospective review of OLT from January 1997 through December 2004. Setting: University of Southern California University Hospital. Patients: A total of 272 OLTs were performed on non-JW adults. This number includes 216 (79.4%) deceased donor and 56 (20.6%) living donor liver transplantations. Thirty-three OLTs were performed before January 2000 (ie, before the initiation of a transfusion-free program) (group 1), and 239 OLTs were performed after January 2000 (group 2). In group 2, all patients underwent OLT using cell-scavenging techniques and acute normovolemic hemodilution whenever feasible. Demographic, laboratory, and clinical data were collected and matched for severity of disease (model of end-stage liver disease [MELD] score). Transfusion records of packed red blood cells (PRBCs), platelets, and fresh frozen plasma (FFP) were obtained from the University of Southern California blood bank. Results: In comparing group 2 with group 1, the mean MELD score was statistically significantly higher (P<.001), whereas the mean number of intraoperative PRBC and FFP transfusions was significantly lower (P = .03 and P = .004, respectively). The number of preoperative and postoperative PRBC, FFP, and platelet transfusions between the 2 groups was not statistically different. Conclusion: The development of a transfusion-free surgical program for JW patients has had a positive impact on reducing the overall blood use in non-JW patients undergoing OLT, despite the increase in MELD score.