OBJECTIVES: To estimate the differences in costs of treating migraine headaches employing a stratified care (STRAT) approach versus the more common stepped care (STEP) using MIDAS scores in the U.S. STRAT using MIDAS scores has been shown to be cost-effective in other settings. However, STRAT is not widely used in the U.S. In this study, a published decision model was adapted to the U.S. setting and the differences in costs were evaluated for STEP and STRAT in the U.S. by differentiating the patients by MIDAS scores.   METHODS: Published values for costs of physician/specialist visits, over the counter (OTC) analgesics, aspirin+metoclopramide (AM), triptans, and hospitalizations were used to create a microsimulation model for a U.S. perspective. Therapy effectiveness for OTCs, AM, and triptans by MIDAS scores I, II, and III were taken from the published decision tree. In the base-case the proportion of MIDAS I, II, and III patients were 5%, 25%, and 70% respectively. STEP patients were forced through each phase of therapy regardless of MIDAS score. STRAT patients were moved ahead to advanced phases of therapy given higher MIDAS score. In the model, a sample of 1000 patients is taken and is distributed according to the MIDAS scores. The costs are attached to each node of the treatment algorithm to obtain the total costs.  RESULTS: Base case results showed that mean annual direct medical costs on STEP for the population were $1229 compared to $1088 for STRAT. Sensitivity analysis showed that the differences in costs (STEP-STRAT) were $210 for a cohort of MIDAS II patients and $142 for a cohort of MIDAS III patients.  CONCLUSIONS: Model results indicate that STRAT has the potential for cost savings in a U.S. setting. Increased awareness and used of STRAT can benefit patients, providers, and payers in the treatment of migraine headache.