OBJECTIVES: To evaluate the cost-effectiveness of treating patients without traditional risk factors for cardiovascular disease with statins. METHODS: Cost-effectiveness was evaluated using a backward induction model. A hypothetical cohort of men and women aged 40 to 80 years was evaluated for their first acute myocardial infarction (AMI) or cardiovascular accident (CVA). The Reynolds Risk Score (RRS) was used to generate event risks and risk reductions as the impact of therapy on lipids and c-reactive protein (CRP) could be calculated independently. Covariates for the RRS were adapted from the JUPITER trial and national health statistics. Life expectancies, quality of life adjustments, and event costs for AMI and CVA were ascertained from the primary literature. Direct and indirect treatment costs were based on the primary literature, Adult Treatment Panel III (ATPII) protocols and the Bureau of Labor Statistics. Medication costs were adapted from the Federal Supply Schedule. Costs were inflated to 2009 US$ using the medical component of the CPI and discounted at a rate of 3%. A sensitivity analysis was also performed. RESULTS: Using a threshold of $150,000 per QALY, treatment was cost-effective with generic statins in all men and women, aged 40 to 80 years when both CRP and LDL levels were affected.  It was cost-effective to treat men > 60 years with a hypothetical medication that only affected CRP levels.  In the base case (65 year old men/women), the model was sensitive to adherence, smoking status (women), premature family history of AMI, brand rosuvastatin price, and the level of LDL reduction. CONCLUSIONS: In this population, it is cost-effective to treat all patients for the primary prevention of AMI and CVA with a generic statin that confers therapeutic benefits similar to what was modeled in this study. Selectively lowering CRP levels is only cost-effective in males > 60 years.