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Preoperative epoetin alfa administration decreases transfusion requirements and may reduce transfusion complications, such as postoperative infection due to immune suppression and thus hospitalization time. This study examined the impact of preoperative epoetin alfa administration on postoperative recovery and infection rate.In an open randomized controlled multicentre trial in patients undergoing orthopaedic surgery, the effects of preoperative administration of epoetin alfa vs. routine care were compared in six countries. Haemoglobin (Hb) values, transfusions, time to ambulation, time to discharge, infections and safety were evaluated in patients with preoperative Hb concentrations 10-13g dL−1 (on-treatment population: epoetin n = 460; control n = 235), from study entry until 4-6 weeks after surgery. Outcome was also compared in patients with and without transfusion.Epoetin-treated patients had higher Hb values from the day of surgery until discharge (P < 0.001) and lower transfusion rates (12% vs. 46%; P < 0.001). Epoetin treatment delivered no significant effect on postoperative recovery (time to ambulation, time to discharge and infection rate). However, the time to ambulation (3.8 ± 4.0 vs. 3.1 ± 2.2 days; P < 0.001) and the time to discharge (12.9 ± 6.4 vs. 10.2 ± 5.0 days; P < 0.001) was longer in the transfused than in the non-transfused patients. Side-effects in both groups were comparable.Epoetin alfa increases perioperative Hb concentration in mild-to-moderately anaemic patients and thus reduces transfusion requirements. Patients receiving blood transfusions require a longer hospitalization than non-transfused patients.