OBJECTIVES: Statin monotherapy is the mainstay of LDL-C management for CHD patients in Portugal, however several therapeutic options are available and predicted to have different clinical and economical impact. This analysis estimates the Cost-Effectiveness (CE) of adding ezetimibe 10 mg (EZ10) to generic atorvastatin 10/20 mg (A10/20) against generic atorvastatin titration (A20/40) and against switch to rosuvastatin 10/20 mg (R10/20) in Portuguese CHD patients who are currently above LDL-C goal (≥2.5mmol/L). METHODS: The analysis was based on a previously published Markov model, employed to evaluate the life-time costs and health outcomes, including life-years (LY) and quality adjusted life-years (QALY). The model incorporated Framingham risk equations, Portuguese population characteristics, CHD event rates, quality of life estimates, local resource use and due unit costs. RESULTS: From 18 CHD patient risk profiles, discounted lifetime costs per patient with A20/40, R10/20 and A10/20+EZ10 treatment were €20,987, €23,134 and €25,476, respectively. Average gain with A10/20+EZ10 were 0.43 LY and 0.17 QALY versus A20/40; and 0.38 LY and 0.15 QALY versus R10/20. Thus, the incremental costs per QALY gained by switching patients from A10/20 to A20/40+EZ10 were €26,435 and €15,907 against titrating to A20/40 and switch to R10/20, respectively. Based on the Portuguese CE acceptability frontier with a willingness-to-pay value of €30.000/QALY gained, A10/20+EZ10 is projected to be CE for CHD patients on secondary prevention. CONCLUSIONS: In the Portuguese CHD patients not at LDL-C goal treated with A10/20, adding EZ10 is CE when compared with atorvastatin titration or switching to rosuvastatin. Moreover, the expected erosion of atorvastatin generics' price will favor CE ratio of A10/20+EZ10 versus R10/20 switch. Thus, ezetimibe is effective in lowering LDL-C, and based on the analysis conducted, is projected to reduce CV events, improve quality of life, and is cost-effective by commonly used criteria in Portugal.