Background: The effects of stem cell therapy in myocardial infarction (MI), especially about long-term outcomes, are still mostly unknown. We report long term follow-up results of randomized clinical trial of granulocyte colony-stimulating factor (G-CSF) based peripheral blood stem cell therapy. Methods and Results: In MAGIC Cell-3-DES trial, we evaluated long term outcome of MI patients in cell infusion group (57 and 22 patients with acute and old myocardial infarction respectively) and control group (60 and 24 patients with acute and old myocardial infarction respectively). Median follow up duration is 41.5months. Occurrences of cardiac death, MI, hospitalization due to heart failure, angina and revascularization were significantly reduced in cell infusion group compared with control group during follow-up (event rate: 12.7 % vs. 29.8 %, Hazard ratio = 0.404, 95% confidence interval: 0.182-0.896, p=0.026). G-CSF based stem cell therapy has sustained vascular protective effects during 4 years follow-up duration as suggested in previous studies shown promoted endothelial healing by G-CSF in animal study, vascular remodeling by IVUS, and G-CSF mediated restoration of endothelial dysfunction in MI patients (event rate: 10.1 % vs. 23.8 %, Target-vessel revascularization: Hazard ratio = 0.361, 95% confidence interval 0.149-0.875, p=0.023). In patients with acute myocardial infarction, left ventricular ejection was significantly improved in cell infusion group but not in control group at 6 months follow-up (from 51.2 짹 9.7 % at baseline to 53.8 짹 8.6% vs. from 51.7 짹 13.1 % to 52.8짹 11.9%, p=0.04). Although the degree of improvement in left ventricular systolic function is maintained, its statistical significance was not maintained at 24 months follow-up mostly due to incomplete MRI follow-up rate (54.0짹 14.1% vs. 53.3짹 11.7%, p=0.06). These results suggested that stem cell therapy at least promote functional recovery and improved clinical outcomes in long term follow-up. There was no significant difference in occurrence of serious non-cardiac adverse reaction between cell infusion and control group. Conclusions: Peripheral blood stem cell therapy promotes functional recovery and improves clinical outcomes in long term follow-up of patients with myocardial infarction. This result suggested that stem cell therapy can be considered therapeutic options for patients with myocardial infarction.