This multicenter study was designed to clarify the positive effects of recombinant human erythropoietin (EPO; epoetin alfa) by subcutaneous administration on anemia after autologous blood donation in cardiac surgery. A total of 55 patients undergoing elective heart surgery were enrolled in this study and subcutaneously given EPO at a dose of 200IU/kg (200IU group, <i>n</i>=23), 400IU/kg (400IU group, <i>n</i>=16) or 600IU/kg (600IU group, <i>n</i>=16) once a week for 3 weeks prior to surgery. Autologous blood (400g) was drawn twice from each patient, at 14 days and 7 days before surgery. Oral iron was given daily throughout this study. The mean reticulocyte counts increased significantly 2 weeks after the first administration of EPO in the 200IU group or 1 week after the first administration in the 400IU and 600IU groups. There was an increase in mean hemoglobin (Hb) levels 1 week after the initiation of EPO by 1.7, 2.8 and 2.1% in the 200IU, 400IU and 600IU groups, respectively. After the first drawing of autologous blood, the Hb levels decreased gradually in all groups despite the second administration of EPO. The change in Hb level immediately before surgery however, was a 4.2% decrease (<i>p</i><0.05) in the 200IU group and 0.8% decrease (N. S.) in the 400IU group and 0.7% increase (N. S.) in the 600IU group in comparison with the initial Hb level. In conclusion, subcutaneous administration of EPO was effective in improving anemia after autologous blood donation in cardiac surgery.