Background: Optimal medical therapy after acute myocardial infarction was expected to improve clinical outcomes. However, there were few studies to analyze the pattern and clinical impact of optimal medical therapy according to the risk stratification Methods: A total of 9050 hospital survivors with AMI who did not have any contraindications to antiplatelet agents, 棺-blocker, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEi/ARB), and statin were enrolled in a nationwide prospective Korea Acute Myocardial Infarction Registry (KAMIR) between Nov 2005 and Jan 2008. Risk stratification was performed using with the Global Registry of Acute Coronary Events (GRACE) score, and classified as low (n=3527, 39.0%), intermediate (n=3547, 39.2%), high risk (n=1976, 21.8%) groups. Optimal medical therapy was defined as the use of all indicated medications adherently after discharge. Primary end points were a composite of all cause of death, and myocardial infarction during 6-month clinical follow-up. Results: During six months follow up, the primary end points occurred in 250 patients (2.8%). Use of dual-platelet agent (aspirin, clopidogrel; 93.7% vs. 87.1%, p<0.001), 棺-blocker (73.2% vs. 66.5%, p<0.001), ACEi/ARB (81.2% vs. 78.4%, p=0.018), and statin (76.2% vs. 67.5%, p<0.001) were significantly decreased in high risk patients compared with low to intermediate risk groups. Optimal medical therapy was performed in 4189 patients (46.3%). Optimal medical therapy after discharge improved clinical outcomes in patients with AMI [Hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.49-0.83, p=0.001], and high risk patients according to GRACE score (HR 0.62, 95% CI 0.44-0.89, p=0.009). However, no significant differences was existed in low to intermediate risk groups (HR 1.00, 95% CI 0.67-1.49, p=0.985). Conclusions: KAMIR registry demonstrated that patients with AMI at higher risk are least likely to receive optimal medical therapy. Quality improvement strategies are needed to enhance the therapeutic benefit for post-discharge AMI patients especially in high risk patients according to the GRACE score.