Background: Cytokine treatment has angiogenic, cytoprotective and stem cell mobilizing effects. It has been regarded as a promising therapeutic modality for ischemic heart disease. Although G-CSF treatment alone showed excellent therapeutic efficacies in animal study, outcomes in clinical studies are mostly disappointing. To improve the angiogenic and stem cell mobilizing efficacy of cytokine, we evaluated combination treatment with erythropoietin and G-CSF in comparison with G-CSF alone in patients with acute myocardial infarction. Methods and Results: This is a sub-study of MAGIC Cell-5-combicytokine trial. We randomized 65 patients with acute myocardial infarction into the combination treatment group with erythropoietin and G-CSF (n=44) and the G-CSF treatment alone group (n=21). After revascularization, G-CSF was treated for 3days with dose of 10ug/kg/day in both groups and single injection of 4.5ug/kg (maximum 300ug) of darbepoeitn was administrated at the first day in combination cytokine group. Peripheral blood stem cells were obtained by apheresis for intracoronary infusion at day 4 (1day after completion of cytokine treatment). Peripheral blood, obtained just before apheresis, and apheresis cell products were analyzed by FACS. In peripheral blood, combination cytokine group showed higher proportion of angiogenic cells in compared to G-CSF group including CD3+CD31+ angiogenic T cells and CD73+cells. Interestingly, apheresis products showed different cell compositions compared to peripheral blood. The combination cytokine group showed higher Tie2+ cells in apheresis product compared to the G-CSF group. Conclusion: Combination treatment with erythropoietin and G-CSF is more effective for mobilizing angiogenic cell population compared to G-CSF alone in patients with acute myocardial infarction. These results suggest that combination cytokine treatment may have superior angiogenic therapeutic efficacy to G-CSF alone.