OBJECTIVES: Clinical evidence on statins has demonstrated that considerable differences exist among various statins regarding clinical efficacy and safety. These differences can lead to dissimilar economic outcomes from drug therapy using one brand of statin over another. The objective is to estimate the cardiovascular events reduction and subsequent cost savings (direct and indirect costs) of rosuvastatin versus atorvastatin in hypercholesterolemia treatment from a Canadian perspective. METHODS: Benefits of reducing LDL-C was incorporated into a model to calculate reduction in cardiovascular (cardiac and cerebrovascular) events and resulted economic outcomes. Data for LDL-C reduction from a head-to-head RCT [Am Heart J 2002;144:1044-51]; rosuvastatin (starting 10mg) versus atorvastatin (starting 10mg) with up-titration doses; and distribution of cardiovascular risk for users [N=100,000, duration 5 years] in the Canadian population [Clin Invest Med 2007;30:E63-E69]. RESULTS: Rosuvastatin and atorvastatin can prevent 3996 (95%CI) (2801 to 5564) and 3306 (2295 to 4643) deaths, respectively. Furthermore, cardiovascular events (non-fatal MI and stroke) can be reduced using rosuvastatin and atorvastatin by as many as 10,518 and 8,702, respectively. [Number of non-fatal MI and stroke can be prevented by rosuvastatin are 7193 (5092 to 8902) and 3325 (2384 to 4195), respectively. Number of non-fatal MI and stroke that can be prevented by atorvastatin are 5951 (4172 to 7430) and 2751 (1953 to 3501), respectively.] Reduction in cardiovascular morbidity that can be translated to CDN$299,129,432 (199,178,100 to 349,942,318) and $230,980,624 (163,250,686 to 291,973,791) direct cost savings for the Canadian health care system. Total indirect cost savings from cardiovascular mortality and morbidity reduction due to rosuvastatin and atorvastatin therapy were estimated to be as much as $403,824,733 (254,618,972 to 992,132,183) and $311,823,842 (196,610,707 to 829,205,566), respectively. CONCLUSIONS: This modeling study demonstrates that rosuvastatin and atorvastatin produce dissimilar clinical outcomes that can lead to diverse economic outcomes of hypercholesterolemia treatment with these drugs.