Objective.-To examine the direct medical costs associated with migraine, when diagnosed alone and in conjunction with anxiety and/or depression in adults and children.Background.-Migraine is a common disorder that can often be accompanied by comorbid anxiety and/or depression. Given the prevalence of migraine and the likelihood for comorbid conditions, it is not surprising that migraine is extremely costly for society.Methods.-Migraine cohorts were identified in a 1999-2000 database capturing inpatient, outpatient, and prescription drug services from approximately 45 large employers. Four cohorts of adults (migraine only, migraine and anxiety, migraine and depression, migraine and both conditions), and two cohorts of children (migraine only, migraine and anxiety and/or depression), were compared to respective "healthy" cohorts. t-statistics were used to capture differences in costs between the migraine cohorts and the healthy cohorts whereas ANOVA was used to test for differences in costs between subgroups of migraine sufferers.Results.-Compared to nonmigraineurs, adults and children with migraine had significantly higher total direct medical costs in all examined categories (P < .0001) ($7,089 vs $2,923 adults; $4,272 vs $1,400 children). For adults, the presence of depression and/or anxiety along with migraine equated to significantly greater total direct medical costs when compared to their matched healthy cohorts (P < .0001) ($12,642 vs $5,179 anxiety; $11,290 vs $3,135 depression). Children with migraine and either anxiety or depression (or both) incurred an average of $9,875 in total direct medical costs as compared with only $1,165 for healthy comparators. For children and adults, the presence of comorbid anxiety or depression was associated with significantly higher medical costs when compared to migraine alone (P < .0001).Conclusions.-This analysis quantifies the economic impact of a migraine diagnosis for both adults and children. The results of this analysis demonstrate that individuals identified as migraineurs have significantly higher medical costs than healthy comparators, with or without comorbid anxiety and/or depression. This study also suggests that clinicians should be aware that while proper treatment of migraine with effective acute and prophylactic therapy is important, attention must also be directed to comorbid conditions.