OBJECTIVES: A US multi-center study of Epoetin Alfa versus pre-operative autologous donation (PAD) in patients undergoing major orthopedic surgery showed that Epoetin Alfa reduced the risk of allogeneic transfusion. In addition, patients receiving Epoetin Alfa had higher post-operative hemoglobin levels than PAD patients. We examined 1) whether higher post-operative hemoglobin levels are associated with a reduced post-operative length of stay; and 2) the relationship between treatment assignment and post-operative stay. METHODS: Analyses were stratified by type of surgery (hip or knee). Multivariate analysis was used to explore the relationship between post-operative hemoglobin levels and post-operative length of stay. The relation between treatment assignment and post-operative stay was examined using both univariate and multivariate analysis. RESULTS: We found a relationship between post-operative hemoglobin levels and post-operative length of stay in the patients undergoing knee replacement, but not among hip patients. In the univariate analysis, there was no difference in post-operative stay between the Epoetin alfa group and the PAD group among hip patients (4.91 ? 2.07 days versus 4.90 ? 2.66 days). Among knee patients, the post-operative length of stay in the Epoetin alfa group was 4.27 ? 1.60 days, significantly lower than in the PAD group, 4.70 ? 1.80 days (p=.044). Multivariate analysis confirmed these findings. CONCLUSIONS: In addition to reducing the exposure to allogeneic blood, Epoetin Alfa significantly reduced post-operative length of stay when compared to pre-operative autologous donation among patients undergoing knee replacement surgery. The absence of a similar effect among patients undergoing hip replacement may be explained by the finding that post-operative hemoglobin level is not a predictor of post-operative length of stay among these patients.