The effects of subcutaneous administration of recombinant human erythropoietin (EPO) on harvesting autologous blood predonation (ABP) and decreasing homologous blood transfusion (HBT) in open-heart surgery were examined prospectively in 132 patients treated in a 32-institute multicenter study. Single doses of 6000, 12,000, 18,000 and 24,000 unit (IU) of EPO with intravenous iron (40 mg) were administered once a week for 3 weeks with ABP (400 ml/week) before surgery. ABP volume (ml), change of blood hemoglobin level (C-Hb), preoperative net blood hemoglobin increase (delta Hb [g/dl] including ABP, perioperative blood loss (ml), and HBT rate, were as follows; [table: see text] Preoperative reduction of Hb (C-Hb) was less in administration dose of 18,000 IU and 24,000 IU than 6000 IU (p < 0.05). The increase of delta Hb was highest in 18,000 IU and HBT rate was lowest in administration dose of 24,000 IU, however, there was no statistical difference. In conclusion, both 18,000 IU and 24,000 IU of EPO treatment is effective to minimize the progression of anemia according to ABP for open heart surgery.