OBJECTIVES: To compare the cost and effectiveness of combination therapy with ezetimibe vs. doubling of statin dose for high risk patients who failed to reach target LDL cholesterol (LDL-C) levels on their current statin dose. METHODS:  A previously developed Markov model was utilized to evaluate cost and number of cardiovascular events of a high risk cohort in a certain time (3,5,10 years) in the future. The lipid-lowering effects of the addition of ezetimibe (10mg) on top of statins (simvastatin 40mg, atorvastatin 20mg, rosuvastatin 10mg) (E+S, E+A, E+R) vs. doubling of existing statin dose (simvastatin 80mg, atorvastatin 40mg, rosuvastatin 20mg) (2S, 2A, 2R) were estimated from the medicine specification of ezetimibe and researches published. 635 patients were in the high risk cohort who failed to reach target LDL cholesterol (LDL-C) levels on their current statin dose. Patient profile data were generated based on the DYSIS study in China. Data about cost of different cardiovascular events was from published research. Prices of statins and ezetimibe were from NDRC. All costs were calculated in RMB. RESULTS:  In 3,5,10 years after 6-week treatment, combination therapy with ezetimibe could reduce number of non-fatal CHD events, non-fatal stroke and CVD deaths more than doubling of existing statin dose. In 10 years, E+S can reduce non-fatal CHD events by 16.78% than 2S; E+R can reduce non-fatal stroke and CVD deaths by 8.75%, 11.36% than 2R.  In 10 years overall medical expense of combination therapy with ezetimibe is less than doubling of existing statin dose.  CONCLUSIONS: Adding ezetimibe to statin (simvastatin, atorvastatin, rosuvastatin) among high risk patients who were not at LDL-C goal could be a cost-effective treatment strategy when compared to doubling of statin dose.