Background: Only limited data are available for the recent trend of optimal evidence-based medical therapy at discharge after an acute myocardial infarction (AMI). The purpose of this study was to evaluate (1) the temporal in trends (2005-2009) in the use of aspirin, beta-blockers, angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin II receptor blockers (ARB), lipid-lowering agents, and combinations thereof, in post-MI survivors; (2) patient and baseline characteristics associated with optimal medical therapy at discharge. Methods: The Korea AMI Registry I (KAMIR; November 2005-December 2007) and II (KORMI; January 2008-June 2009) were multicenter observational studies of 22,603 patients admitted for AMI. We examined the discharge medications among 14,358 post-MI survivors who did not have any documented contraindications to anti-platelet drugs, beta-blockers, ACE-I/ARBs or statins in 7 periods by 6-month interval. Optimal evidence-based medical therapy was defined as the use of all 4 indicated medications. Results: Of these patients, 7,672 (53.4%) received all 4 medications at discharge. The discharge prescription rates of anti-platelet agents, beta-blockers, ACE-I/ARBs and statins were 99.6%, 75.0%, 82.2%, and 78.9%, respectively. There were significant increases in the discharge use of all 4 indicated medications over time (23.5% relative increase); 50.4% and 59.0% of patients in KAMIR and KORMI Registries, respectively, were prescribed optimal medical therapy (p <0.001). Although consistent increases in the use of each of the 4 indicated medications were observed over time, particularly marked relative increases in the use of beta-blockers (14.3% relative increase) and statins (6.9% relative increase) were noted. In multivariate analysis, advanced age, higher Killip class at admission, left ventricular systolic dysfunction, higher serum creatinine levels, history of previous coronary heart disease, and coronary artery bypass grafting during hospitalization were independently associated with less use of optimal medical therapy. In contrast, enrollment in KORMI Registry (versus KAMIR) in addition to higher systolic blood pressure, higher total cholesterol levels, prior hypertension, presence of ST elevation, and percutaneous coronary intervention during hospitalization were independently associated with the use of optimal medical therapy. Conclusions: There were considerable improvements in the use of all 4 indicated medications over time. However, the optimal medical therapy is prescribed at suboptimal rates, particularly in patients with high-risk features. Educational to improve use of these therapies could further enhance the prescription rates in post-MI patients.