OBJECTIVES Compare predicted incremental reduction in hospital days and associated costs in managed health care (MHC) mixed dyslipidemia patient cohort treated with fixed-dose niacin extended-release and simvastatin (NER+S) therapy. METHODS Two hypothetical formularies were modeled, a baseline formulary which did not include NER+S and an adjusted formulary which did. Other lipid therapies included all marketed branded medications. The model was developed using product labeling, clinical trial results, national prescription claims data, and a risk equation derived from the HealthCore Integrated Research Database to estimate the incidence of cardiovascular disease (CVD) events and associated hospital days avoided among patients achieving and not achieving optimal lipid values for LDL-C, HDL-C, and triglycerides (TG). Study patients included those aged ≥18 years with sub-optimal baseline LDL-C ≥ 100 mg/dL, HDL-C ≤ 40 mg/dL for males; ≤ 50 mg/dL for females, and/or TG levels ≥ 150 mg/dL for females/diabetics; ≥ 200 mg/dL for males/non-diabetics. A cost-effectiveness analysis was performed over three years evaluating the incremental cost per hospital-day avoided after addition of NER+S to current formulary. RESULTS Among 1,000,000 patients, 529,620 primary and secondary risk patients (52.96%) aged ≥ 18 years were identified. Mean age at baseline was 54 ± 11 years and 45% was female. Over 3 years, there was reduction of 157 hospital days after addition of NER+S versus current formulary (54,839 vs. 54,997 days) along with a reduction of $4,888,916 in total costs (sum of health plan costs, copayment, drug-monitoring costs, and CVD-event related costs) [$1,337,787,345 vs. $1,342,676,261], thus achieving an incremental cost-saving of $31,041 per hospital day avoided. CONCLUSIONS The MHC database-based model predicts that treating sub-optimal HDL-C and TG beyond achievement of optimal LDL-C goals may result in healthcare resource savings to a MHC organization after the addition of NER+S to a managed care formulary.