A multicenter, double-blind, placebo-controlled, parallel-group study was undertaken to determine whether Epoetin alfa can reduce perioperative transfusion requirements. Twenty-six medical centers enrolled 316 patients who were scheduled for major orthopedic surgery and were expected to require > or = 2 units of blood. Patients were stratified according to baseline hemoglobin levels and randomly assigned to receive either Epoetin alfa (300 IU/kg or 100 IU/kg) or placebo for 15 consecutive days starting 10 days prior to, on the day of, and for 4 days after surgery. Epoetin alfa (300 IU/kg) resulted in significantly less exposure to allogeneic blood transfusion compared with placebo (16%) versus 45%) in patients whose baseline hemoglobin level was > 10 to < or = 13 g/dL (P = 0.024). Mean number of units transfused per patient was also lower among those treated with Epoetin alfa (overall, P = 0.027). Epoetin alfa was safe and well tolerated in this population.