OBJECTIVE: The purpose of this study was to determine the indirect cost burden associated with migraine. METHODS: Data were obtained from Thomson-Medstat's Health and Productivity Management (HPM) database for the 2002 through 2003 calendar years. The migraine cohort was composed of patients who had a diagnosis of migraine or migraine-specific abortive prescription medication, or both. A control cohort of patients without migraine was matched to patients in the migraine cohort. The average annual indirect burden of illness (BOI) of migraine and a national indirect BOI were estimated. RESULTS: Annual indirect expenditures were significantly higher in the migraine group compared with the control group ($4453 vs $1619; P<0.001). The national annual indirect BOI, excluding presenteeism, was estimated to be $12 billion (mostly attributed to absenteeism). CONCLUSIONS: Migraine imparts a substantial indirect cost burden. Projected to a national level, this amounts to an annual cost to US employers of approximately $12 billion.