INTRODUCTION Coronary heart disease (CHD) is a leading cause of death in the Western world. Hypercholesterolemia is an important risk factor for CHD. Ezetimibe, a cholesterol absorption inhibitor, can be used in combination with statins to improve cholesterol levels. OBJECTIVES: The aim was to assess cost-effectiveness of ezetimibe combined with simvastatin compared to atorvastatin or simvastatin monotherapy for second line treatment of primary hypercholesterolaemia in the Dutch population.    METHODS: A published Markov model (Cook et al 2004) was adapted to evaluate two lipid treatment scenarios in the Netherlands. Baseline patient data from the Dutch EASEGO study were used. The first scenario was based on this study: patients not reaching low-density-lipoprotein cholesterol (LDL-C) goal on atorvastatin 10mg (A10) or simvastatin 20mg (S20) were included. These patients were modeled using a doubled dose, or addition of ezetimibe 10mg to generic simvastatin (eze10/sim20). The second scenario was based on Dutch guidelines. All patients were not meeting their LDL-C goal on simvastatin 40mg (S40) and were switched to atorvastatin 40mg (A40), or ezetimibe 10mg was added to generic simvastatin (eze10/sim40). Key effectiveness measure was change in ratio of total cholesterol to high-density-lipoprotein cholesterol. Model parameters were derived from published literature and guidelines. One-way sensitivity analyses were performed for key model parameters. RESULTS: Based on EASEGO the incremental cost-effectiveness ratio for eze10/sim20 was €3,497 per quality-adjusted life year (QALY) compared to A20 and €26,417/QALY compared to S40. Based on Dutch guidelines, eze10/sim40 was dominant, and can be seen to be cost-saving compared with A40 (- €3,675/QALY). These results were not very sensitive to changes in input parameters CONCLUSIONS: Eze/sim can be considered a cost-effective treatment (EASEGO versus A20 or S40) and in light of the Dutch guidelines (versus A40) even cost-saving. The addition of ezetimibe to simvastatin is a valuable second line treatment option.