Background: The role of adjunctive therapy to stem cell therapy for improving efficacy in patients with myocardial infarction is unknown. Methods: In MAGIC Cell-5 combicytokine trial, we evaluated effects of intracoronary infusion of mobilized peripheral blood stem cells (PBSC) by G-CSF with/without darbepoetin. We randomized patients with acute myocardial infarction who underwent revascularization of infarct related artery into 3 groups and completed 6months follow-up: control (n=27), PBSC (n=28), and combicytokine group (n=54). Both the PBSC and the combicytokine group received G-CSF injection for 3days to mobilize PBSCs and intracoronary infusion of collected PBSCs. Additionally the combicytokine group received single bolus infusion of high dose darbepoetin during revascularization. We evaluated the change of cardiac MR parameters at 6months follow-up. Results: Combicytokine (G-CSF + darbepoetin) is more effective than G-CSF alone in mobilization of PBSCs with angiogenic potentials(P<0.05). At 6months, both PBSC and combicytokine treatment is more effective for reducing infarct size (p<0.05) and restoring regional wall motions (p<0.05) than conventional treatment. And PBSC infusion with darbepoetin is effective for preventing adverse ventricular remodeling (p<0.05) and improving global systolic function in the poor risk patients with reduced LVEF at baseline p<0.05) and microvascular obstruction in baseline MR (p<0.05). Occurrence of adverse event and clinical outcome is not significantly different among 3 groups during 6months follow-up (p>0.05). Conclusion: PBSC infusion with/without darbepoetin is effective for reducing infarct size and restoring regional wall motions in patients with acute myocardial infarction. And combicytokine treatment shows potentials to improve efficacy of PBSC therapy, especially in poor risk patients.