Background: The potential benefits and risks of the use of dual anti-platelet therapy (DAT) beyond 12 months in patients receiving drug-eluting stents (DES) with acute myocardial infarction (AMI) have not been clearly established. Methods: We analyzed 795 patients who had undergone DES implantation with AMI and had been free of major adverse cardiac or cerebrovascular events at least for 12 months in prospective multi-center registry (Infarct Prognosis Study). The duration of DAT was categorized in group 1 (N=185): ��� 12 months and group 2 (N=610): > 12 months. The incidence of cardiac death or recurrent MI was compared between 2 groups. Results: The median duration of follow up was 28.4 months. The Kaplan Meier analysis indicated a benefit of group 2 compared with less than group 1. (2.5 % vs. 8.6 %, log rank test p ���0.001). Continuation of DAT beyond 12 months showed the significant reduction of cardiac death or recurrent MI in Cox proportional hazards analysis even after controlling of confounding variables (Hazard ratio 0.20; 95 CI, 0.09 to 0.42, Cox-model p���0.001). There was no significant difference in the major bleeding between 2 groups. Conclusions: The prolonged (> 12 months) DAT was related with improvement of clinical outcomes in terms of cardiac death or recurrent MI. These findings should be confirmed through larger randomized clinical trials.