OBJECTIVES: Effective cholesterol-lowering therapy is needed in order to reduce the risk of cardiovascular disease in patients with high levels of LDL-cholesterol, especially in high-risk groups such as patients with diabetes or a history of heart disease. Clinical trials have showed that rosuvastatin is an effective cholesterol-lowering medication, but it is also important to assess its cost-effectiveness. METHODS: The cost-effectiveness of cholesterol-lowering therapy with rosuvastatin compared to atorvastatin, simvastatin, and pravastatin was estimated with a Markov model of cardiovascular disease. The model simulated the occurrence of revascularization procedures, myocardial infarction, and stroke. Health effects were measured in terms of quality adjusted life years (QALYs). RESULTS: Cholesterol-lowering therapy with rosuvastatin was found to be cost-saving and associated with better effect (QALYs) compared to atorvastatin and pravastatin. For patients with prior heart disease and no additional risk factor incremental cost per QALY gained of rosuvastatin 10 mg compared to simvastatin 20 mg was 825,000 SEK for 70 year-old men, and 901,000 SEK for 70 year old women. For patients with both coronary heart disease and diabetes the cost-effectiveness ratios compared to simvastatin were 415 000 SEK per QALY for 70 year-old men, and 459,000 SEK per QALY for 70 year-old women. CONCLUSION: The results indicate that cholesterol-lowering therapy with rosuvastatin is cost saving compared to atorvastatin and pravastatin among patients with prior coronary heart disease or diabetes. Compared to simvastatin cholesterol-lowering therapy with rosuvastatin could be cost-effective under certain conditions, in particular in high risk patients with two or more risk factors for cardiovascular disease.