OBJECTIVES: To model the impact of the addition of fixed-dose niacin extended-release and simvastatin (NER/S) therapy to a health plan formulary in terms of optimal low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglyceride (TG) value attainment. METHODS: Two hypothetical formularies with all major branded and generic lipid drugs were modeled over a three year time horizon: a formulary not including NER/S (current formulary) and a formulary which did (revised formulary). Primary and secondary risk patients with ≥1 sub-optimal lipid parameter were sampled from the HealthCore Integrated Research Database between 1/1/2000 and 2/28/2005. Package insert efficacy of antihyperlipidemic medications in each formulary was applied to the sample population. Post-treatment lipid values were evaluated according to U.S. lipid guidelines. Rates of individual and combined optimal lipid value (OLV) [LDL-C, HDL-C, and TG] achievement were estimated in direct proportion to lipid therapy market shares in both formularies. Changes in clinical outcomes between formularies were evaluated relative to incremental change in pharmacy and cardiovascular (CV) disease related medical costs. Market penetration of NER/S was assumed to be 1.5% and payer discounts of 17% and 50% were applied to branded and generic wholesale acquisition costs. RESULTS: The rate of combined OLV attainment over three years in the revised formulary increased 0.57% from the current formulary. Attainment of optimal LDL-C, HDL-C and TG values increased by 0.07%, 0.30%, and 0.10%, respectively. The cost for a 1% increase in optimal LDL-C, HDL-C, and TG attainment was $3,103, $952, and $2,047 respectively. There was an estimated $1,147 cost for every 1% increase in combined OLV attainment. CONCLUSIONS: The addition of NER/S to the health plan formulary increases individual and combined OLV achievement thereby having the potential to reduce the incidence of CV events and CV-related medical costs.