OBJECTIVES: Some high-risk CHD patients have poor outcomes with statin therapy and need to use combination regimens. The combination regimens have not been widely found in cost-effectiveness study. Therefore, this study aimed to analyze the cost-effectiveness of using Simvastatin, Atorvastatin, and Atorvastatin-Ezetimibe combination among high-risk CHD outpatients. METHODS: A cross-sectional retrospective study for 12 months (April 1, 2013 to April 1, 2014) in high-risk CHD outpatients was performed at the Chandrubeksa Hospital Medical Department of the Royal Thai Air Force, Nakhon Pathom, Thailand. The incremental cost-effectiveness ratio (ICER) was determined for cost-effectiveness analysis. The direct medical costs were computed by micro-costing method (Reference price in 2014). The effectiveness outcomes were the percentage differences in LDL-C reduction and the proportion of patients achieving treatment goals (Standard goal (LDL-C < 100 mg/dL) and Aggressive goal (LDL-C < 70 mg/dL)). The cost-effectiveness was concerned on the provider perspective.  RESULTS: There were differences of the direct medical costs between three groups (median ± IQR: 517 ± 149.7, 3,910.4 ± 3,326.5, 13,733.7 ± 3,350.0; p 0.0001, respectively). Simvastatin regimen had the lowest percentage differences in LDL-C reduction when compared to other groups (mean ± SD ;     -20.1 ± 30.1, -28.3 ± 24.2, -38.1 ± 17.1; p 0.0001, respectively). Atorvastatin regimen provide the best cost-effectiveness (ICER = 346.4 THB) by using the proportion achieved standard treatment goal, while Atorvastatin-Ezetimibe combination was dominated. In the case of the aggressive treatment goal showed that Atorvastatin-Ezetimibe combination regimens provided the most cost-effectiveness (ICER 437.7 THB and 1,189.8 THB, respectively).  CONCLUSIONS: Comparision treatment with Simvastatin, Atorvastatin and Atorvastatin-Ezetimibe combination among high-risk CHD outpatients showed that Atorvastatin was more effectiveness and less costly than Atorvastatin-Ezetimibe combination in term of standard treatment goal. While Atorvastatin-Ezetimibe combination was an interesting option when aggressive treatment goal was used.