Objective: Evidence demonstrates a strong association between reductions in LDL-C achieved with statin therapy and reductions in cardiovascular events. Several cost-effectiveness analyses have incorporated LDL-C reduction, which is a "surrogate endpoint", as indicator for effectiveness of interventions in their models. Interpretations of cost-effectiveness analyses with surrogate endpoints may confuse decision-makers. Therefore, clinically important endpoints (hard endpoints) such as cardiovascular events may be a better alternative to comprehend the magnitude of the cost-effectiveness of therapeutics. The objective is to estimate cost savings through cardiovascular event reduction correlated with LDL-C reduction in patients with hypercholesterolemia on statin therapy using pragmatic head-to-head RCTs from a Canadian perspective. Methods: Reducing LDL-C was incorporated into an economic analysis through a reduction in cardiovascular (cardiac and cerebrovascular) events. Data for LDL-C reduction from a head-to-head RCT [Am Heart J 2002;144:1036-43]; rosuvastatin (starting 5mg) versus simvastatin (starting 20mg) with up-titration doses; and distribution of cardiovascular risk for users [N = 100,000, 5 years] in Canadian population [Clin Invest Med 2007;30:E63-E69]. Medical costs are from the perspective of the Canadian health care system. Results: It is estimated that approximate acquisition costs for simvastatin is more than $14 million less than acquisition costs for rosuvastatin. Health care cost-savings through cardiovascular events prevention related to statin therapy are estimated as follows: Non-fatal myocardial infarction, rosuvastatin ($97,488,572) and simvastatin ($88,086,070); ischemic stroke, rosuvastatin ($63,178,674)and simvastatin ($57,085,510). Rosuvastatin saves almost $15.5 (95%CI: $14.8, $16.2) million compared to simvastatin due to cardiovascular events reduction. Rosuvastatin and simvastatin can prevent 3161 and 2857 deaths, respectively. Conclusion: Although the acquisition cost for simvastatin is much less than that for rosuvastatin, the economic benefits of dyslipidemia management with rosuvastatin in the Canadian population is estimated to be significantly superior to simvastatin therapy through a reduction in costs associated with the management of cardiovascular events and sequelae.