Abstract Background Contemporary guidelines documented that optimal medical therapy (OMT) should be prescribed to improve clinical outcome in patients with acute myocardial infarction (AMI). However, the changes of hospital-level variations in prescription rates of OMT for long-term follow-up are unknown. Purpose We aimed to investigate (1) impact of hospital-level variation on the use of each medication and OMT and (2) changes of hospital-level variation in prescription rates of individual medical therapy and OMT during the follow-up. Methods We examined hospital medications of 13,516 AMI patients without documented contraindications to antiplatelet agents, β-blockers (BB), angiotensin-converting enzyme inhibitors (ACE) /angiotensin II receptor blockers (ARB), or statins from the Korean Acute Myocardial Infarction Registry (KAMIR) – National Institute of Health (NIH) database. OMT was defined as use of all 4 indicated medications. Hierarchical generalized linear mixed models estimated hospital-level variation in prescription rates of OMT and each medication after adjustment for patient-level factors. Variation was explored with a median rate ratio (MRR), which estimates the relative difference in risk ratios of 2 hypothetically identical patients at 2 different hospitals. Results The prescription rates of OMT and each effective cardiac medications are presented in Figure. There were substantial decreases in the prescription rates for OMT (from 66.7% to 51.6%) and dual antiplatelet agents (from 99.1% to 50.4%) for 2 years follow-up. After adjustment for patient-level covariates, hospital-level MRR for OMT was 1.47 at discharge, indicating an 47% likelihood that 2 random hospitals would differ in treating identical AMI patients. As the prescription rates of OMT and each effective cardiac medications decreased, adjusted hospital-level MRR for OMT (from 1.47 to 1.22), BB therapy (from 1.35 to 1.15), ACE/ARB therapy (from 1.68 to 1.16), and statin therapy (from 1.19 to 1.06) decreased for 2-year follow-up, whereas MRR for dual antiplatelet therapy increased at 1 year (MRR; 1.61) and 2 years (MRR; 1.63) follow-up (Figure). Among patient-level factors, age >70 years, Killip class>2, obesity, hypertension, previous coronary artery disease, renal dysfunction, reduced ejection fraction, percutaneous coronary intervention was independently associated with the use of OMT. Conclusion Hospital-level variations in the use of OMT and each effective cardiac medications were observed at discharge, but weakened overtime, except for use of dual antiplatelet therapy.