Patients undergoing total knee arthroplasty (TKA) are at high risk for postoperative anemia and allogeneic blood transfusions. Risks associated with allogeneic blood exposure (ie, infection, fluid overload, and longer hospital stays) have prompted alternative blood management strategies. The main goal of this study was to evaluate whether a single change in the clinical blood management of patients undergoing TKA reduced the severity of postoperative anemia or the need for allogeneic blood transfusions. A second goal of this study was to assess the financial impact of the change on the institution. This study compared perioperative cell salvage, preoperative autologous blood donation, and the practice of using allogeneic blood alone in patients undergoing TKA. Clinical and financial data of 154 unique cases of primary TKA at the Mayo Clinic Arizona were retrospectively reviewed. Transfusion rates were 25%, 18%, and 52% respectively for patients in the cell salvage, preoperative autologous blood donation, and allogeneic blood only groups. Respective relative risk reductions were 51.9% (P=.007) and 65.4% (P=.002) with the use of cell salvage or preoperative autologous blood donation versus allogeneic alone. Cell salvage and preoperative autologous blood donation were found to significantly reduce the requirements for allogeneic blood transfusions; these techniques were found to be roughly equivalent in clinical benefit when compared to the use of allogeneic blood alone. The logistical advantages of cell salvage (ie, no preoperative blood donation, no risk of wasting blood units) were associated with greater costs to the institution.