OBJECTIVES: To evaluate the long term cost-effectiveness of rosuvastatin versus generic atorvastatin in the treatment of patients at high cardiovascular risk (CVR) ≥ 5% SCORE or patients with established cardiovascular disease in Spain. METHODS: The efficacy data from STELLAR trial (Statin Therapies for Elevated  Lipid Levels compared Across doses to Rosuvastatin)  was used to simulate cLDL goal attainment at different doses of  rosuvastatin and generic atorvastatin during an initial period of one year. These results were combined in the long term through a Markov model which estimated the number of cardiovascular events and their impact on quality of life in patients at high CVR using the Framingham risk equations. The model estimated quality adjusted life years (QALY) and costs (drug and events costs) up to 20 years. The analysis was conducted from the Spanish National Health System perspective. 3% annual discount rate was applied to costs (€ 2010) and outcomes. Cost-effectiveness was estimated in several subgroups of patients at high CVR according to blood pressure, smoking status, age, cholesterol levels and established cardiovascular disease. RESULTS: In primary prevention of cardiovascular events in patients at high risk, rosuvastatin was a cost-effective option (cost/QALY less than €30,000) versus generic atorvastatin in most of the subgroups analyzed. In patients with established cardiovascular disease, rosuvastatin was a cost-effective option in all males subgroups (ICERs between €4,000 and €18,000 per QALY) and in most of the females subgroups. CONCLUSIONS: The treatment of patients at high cardiovascular risk with rosuvastatin was more effective than generic atorvastatin in terms of survival and quality adjusted survival. Incremental cost-effectiveness ratios were below the commonly accepted efficiency threshold in Spain (€30,000) in most of the defined subpopulations by different combination of risk factors.