OBJECTIVE: To asses the cost-effectiveness of rosuvastatin in comparison with simvastatin and atorvastatin for the treatment of hypercholesterolemia in daily practice in the Netherlands. METHODS: A cohort of statin users was selected from the PHARMO database. Information on cholesterol and medical resource utilization was obtained from a clinical lab database. Information on treatment patterns was obtained from GPs. Effectiveness in daily practice, defined as change in cholesterol level, and achieving the NCEP ATP-II guideline was assessed at 3, 12, and 24 months. The ratio between efficacy from clinical trials and effectiveness in daily practice for simvastatin and atorvastatin combined with the efficacy of rosuvastatin was used to estimate the effectiveness of rosuvastatin in daily practice. With bootstrapping the cost-effectiveness of rosuvastatin was estimated. RESULTS: In daily practice it is expected that rosuvastatin results in a larger reduction in total cholesterol and LDL-cholesterol, and a higher probability of achieving the NCEP ATP-II guidelines than simvastatin and atorvastatin. For diabetes or arteriosclerosis patients the difference in predicted effectiveness was greater: The probability of achieving the LDL-cholesterol threshold for rosuvastatin was 63.9% (95%CI 46.5; 81.3), for simvastatin 37.1% (95%CI 29.8;46.0), and for atorvastatin 41.9% (95%CI 28.0; 62.5). Total medical costs from the insurance perspective were €1471 for rosuvastatin, €1850 for simvastatin, and €1562 for atorvastatin over a 2-year period. The probability that rosuvastatin is dominant over simvastatin is more than 90%. The probability that rosuvastatin is cost-effective in comparison to atorvastatin varies between 60% and 80% depending on outcome, willingness to pay, and risk profile. CONCLUSION: It is expected that rosuvastatin in comparison to simvastatin saves costs in combination with a greater effectiveness in routine daily practice. The results indicate that rosuvastatin is also cost-effective in comparison with atorvastatin. A greater benefit was observed for patients with diabetes and arteriosclerosis treated with rosuvastatin.