OBJECTIVES: To compare the cost effectiveness of adding ezetimibe on top of atorvastatin therapy vs. doubling of atorvastatin dose for high risk patients who failed to reach target LDL cholesterol (LDL-C) levels on their current atorvastatin dose. METHODS: A previously developed Markov model was utilized to evaluate cost and health outcomes converted into quality adjusted life-years (QALY).  The lipid-lowering effects of the addition of ezetimibe (10mg) on top of atorvastatin (20mg) (EZ+A) vs. doubling of existing atorvastatin (10 or20mg to 20 or 40 mg) (2A) doses were estimated from clinical trial data.  High risk cohort was defined as those with established coronary heart disease (CHD) and/or diabetes.  Patient profile data were generated based on the LTAP-2 study in Brazil.  Costs of acute and long-term care for CHD events and treatments were calculated in Brazilian Reals (R$). RESULTS: Discounted costs and QALYs ranged from R$ 13,576 to R$ 57,273 and 5.99 to 15.59 respectively for 2A arm whereas ranges for discounted costs and QALYs were R $15,673 to R$ 60,735 and 6.16 to 15.64 respectively for EZ+A among 54 patients with CHD and/or diabetes.  Incremental cost-effectiveness ratios (ICERs) comparing EZ+A vs. 2A were estimated to range between R$ 13,392 to R$ 75,883 (ICER exceeded R$ 60,000 only for 4 patient profiles). These results suggest that EZ+A was cost-effective against 2A at a threshold of 3 times  Brazilian per capita GDP (~R$ 60,000) for majority of the patients (50 out of 54 patient profiles). In addition, for patients with CHD and diabetes, EZ+A was highly cost-effective (ICER less than Brazilian GDP per capita~ R$ 20,000) against 2A. CONCLUSIONS: Results suggested that adding ezetimibe to atorvastatin among high risk patients who were not at LDL-C goal could be a cost-effective treatment strategy when compared to doubling of atorvastatin dose.