OBJECTIVES: To estimate the direct healthcare cost burden of migraine in a large commercially insured United States (US) population. METHODS: The data source for this study was the MEDSTAT MarketScan database, comprised of medical, pharmaceutical, and enrollment information on employees for 52 employer groups for the calendar year 2004. Subjects with a diagnosis of migraine or use of a migraine-specific abortive drug were identified as the migraine cohort. A random sample of patients without migraine was propensity score matched, based on demographic characteristics and comorbidity index, to the migraine cohort to yield a matched control group. Expenditures between migraine and matched control cohorts were compared to derive the burden of illness attributable to migraine. RESULTS: The analyses included 215,209 subjects in the migraine cohort, and equal number of subjects in the control group. The mean age was 41 ( SD= 13.3), and 82% were female. After matching, the cohorts were similar with respect to age, gender, geographic region, urban residence, insurance type, the number of psychiatric diagnostic groups and Charlson comorbidity index. The migraine cohort incurred significantly higher expenditure than the control cohort in all categories (prescriptions, outpatient, ER, and inpatient). Total health care expenditures were $2571 per patient per year (PPPY) higher in the migraine group ($7007 versus $4436 PPPY in the control group; p<0.001). CONCLUSIONS: The migraine cohort was associated with significantly higher total health care expenditures compared to a matched control, based on recent data from a large sample of commercially insured individuals. This data suggest that US employers are bearing a considerable direct cost burden as a consequence of migraine.