Objective: To determine the economic impact of acute medication overuse among members with migraine or headache enrolled in a large, national managed care organization (MCO). Methods: Commercial MCO members with a diagnosis of migraine or headache and acute medication prescriptions from 2002-2006 comprised the study population. A novel claims-based algorithm based on literature review and clinical expert input was created to establish thresholds of potential overuse. Two cohorts were identified: members with evidence of acute medication overuse (MO) and members without evidence of medication overuse (non-MO). Cohorts were followed over variable time periods and compared on demographics, comorbidities, health care resource utilization and costs. Results: A total of 17,202 individuals met the criteria for medication overuse, 45,659 comprised the non-MO cohort. Most MO patients met the criteria for medication overuse by exceeding the threshold for opiates (62%) or triptans (38%). The MO cohort had significantly greater migraine/headache-related and all-cause resource utilization compared with the non-MO cohort. On a per subject per month basis, all-cause medical costs for the MO cohort were $1236 compared with $185 for the non-MO cohort (<0.0001); all-cause pharmacy costs were $483 for the MO cohort and $105 for the non-MO cohort (<0.0001). For migraine/headache-related medical and pharmacy costs, total medical costs per subject per month were $209 for the MO cohort and $33 (<0.0001) for the non-MO cohort, while pharmacy costs were $286 for the MO cohort and $46 (<0.0001) for the non-MO cohort. Conclusion: Members of this MCO with migraine or headache who overused acute medications utilized more health care resources and incurred greater costs compared with members without acute medication overuse. These results suggest the possibility that alternate treatment strategies that decrease medication overuse may result in less healthcare resource utilization and lower costs.