OBJECTIVES: To examine the direct and indirect costs for adults diagnosed with migraine, as well as the costs associated with comorbid anxiety and/or depression. METHODS: Individuals diagnosed with migraine or receiving a migraine medication between 1999-2000 were identified in a database capturing inpatient, outpatient, and prescription drug services from approximately 45 large employers. The migraine cohort (N=2519) was matched to a non-migraine cohort (N=2519) at a 1:1 ratio based upon age, gender and metropolitan statistical area. Variables of interest included direct medical costs (inpatient, outpatient, and prescription drug) as well as indirect costs (absenteeism, short-term disability and worker compensation). RESULTS: Adults with migraine had significantly higher inpatient (p=0.0008), outpatient (p<0.0001), prescription drug (p<0.0001), and overall medical costs (p<0.0001) compared to the non-migraine cohort. In addition, adults with migraine had significantly higher costs associated with absenteeism (p=0.0010) compared to the healthy cohort. The presence of depression (N=556) or anxiety (N=158) in addition to migraine equated to significantly greater outpatient, prescription drug, and total medical costs compared to a healthy comparator group. The differential in total costs (medical plus productivity) between migraine sufferers with comorbid anxiety ($4562, p<0.0001) or comorbid depression ($6193, p<0.0001) and the healthy cohort was substantially greater than the differential between migraine sufferers without these comorbidities and their healthy matches ($3638, p<0.0001). CONCLUSIONS: These results demonstrate and quantify the economic burden in terms of direct and indirect costs to employers of migraine alone and migraine in conjunction with depression or anxiety.