OBJECTIVE: To determine the cost-effectiveness of rosuvastatin compared to five other statins, from a managed care payer perspective. METHODS: A decision-analytic model compared the 1-year costs and effectiveness of the following six statins, titrated over the specified dose ranges in patients with elevated low-density lipoprotein cholesterol (LDL): atorvastatin 10-80mg, fluvastatin 40-80mg, generic lovastatin 20-80mg, pravastatin 20-40mg, rosuvastatin 10-40mg, and simvastatin 20-80mg. Effectiveness measures included percent change in LDL, high-density lipoprotein cholesterol (HDL), and number of patients achieving National Cholesterol Education Program (NCEP) Second Adult Treatment Panel goal (per 10,000 treated). Effectiveness estimates came from two 52-week, comparative clinical trials and dose equivalence tables. Drug, physician and laboratory resource use were estimated using current NCEP guidelines, then multiplied by Medicare reimbursement rates for services, and wholesale acquisition costs for drugs. Probabilistic sensitivity analyses employed the net health benefits framework and cost-effectiveness acceptability curves were constructed. RESULTS: In the base-case analysis, rosuvastatin dominated atorvastatin, lovastatin, pravastatin and simvastatin. Fluvastatin was least costly but also least effective; rosuvastatin was most effective and had the second lowest cost. Compared with fluvastatin, the incremental LDL-C reduction, HDL-C increase, and percent of patients to goal with rosuvastatin were 16%, 3%, and 27%, respectively. Incremental costs per additional 1% reduction in LDL-C, a 1% increase in HDL-C, and patient to goal were $6, $33, and $353, respectively. Results were robust to probabilistic analyses: in each of 1000 simulated populations of 1000 patients, rosuvastatin conferred more net health benefits than atorvastatin, lovastatin, pravastatin, or simvastatin. Rosuvastatin was the optimal choice among all statins when willingness to pay for an additional 1% decrease in LDL, 1% increase in HDL, and patient to goal exceeded $6, $37, and $353, respectively. CONCLUSIONS: Rosuvastatin is less costly and more effective than atorvastatin, lovastatin, pravastatin and simvastatin; and highly cost-effective compared with fluvastatin.