OBJECTIVES: To evaluate the short-term cost-effectiveness of achieving multiple optimal lipid values (MOLV) for  fenofibric acid (FFA) co-administered with low-cost generic simvastatin (20mg and 40mg) compared to co-administration with branded rosuvastatin (10mg and 20mg) or atorvastatin (20mg and 40 mg) in post-menopausal female, elderly (age ≥65 years), metabolic syndrome, and diabetic patient subgroups with mixed dyslipidemia.  METHODS: A disease outcomes model was used to estimate MOLV attainment (achieving any 3 of 4 targets: total-C <200mg/dL, LDL-C <130mg/dL, HDL-C >40mg/dL or >50mg/dL pending subgroup, TG <150mg/dL) and associated annual drug costs for patients receiving FFA and a statin. Subgroup-specific baseline lipid values, lipid efficacy, and adherence rates were obtained from pooled analyses of three 12-week, double-blind, randomized controlled trials of FFA co-administered with a statin.  FFA and statin costs were based on wholesale acquisition costs net of patient copayments.  RESULTS: The predicted proportion of patients achieving MOLV for FFA co-administered with moderate-dose simvastatin, rosuvastatin, and atorvastatin ranged from 39%-68%, 56%-90%, and 50%-80%, respectively, across the four patient subgroups. Corresponding per patient drug costs ranged from $859-$886, $1730-$1822, and $1718-1896, respectively, and per patient costs to achieve MOLV ranged from $1281-$2266, $1926-$3195, and $2299-$3415, respectively. The incremental cost effectiveness ratio (ICER) for one additional patient achieving MOLV for FFA co-administered with moderate-dose rosuvastatin or atorvastatin versus generic simvastatin was $6,376 and $20,552 in post-menopausal female; $3,937 and $7,926 in elderly; $5,272 and $8,869 in metabolic syndrome; and $5,412 and $7,426 in diabetic patient subgroups, respectively. For low-dose statin combinations, qualitative results were similar though ICERs were higher in the elderly and diabetic patient subgroups. CONCLUSIONS: Co-administration of FFA with low-cost generic simvastatin results in slightly fewer patients achieving MOLV but has the lowest annualized cost per MOLV achieved compared to equivalent dose combinations with rosuvastatin or atorvastatin in special populations.