OBJECTIVES: Approximately 120 million Americans suffer from migraines, leading to impaired functional capacity and substantial societal costs. Studies have shown that migraine sufferers use more healthcare resources than non-migraine sufferers. This study compares healthcare resource use among migraineurs receiving various drug treatments. METHODS: Fee-for-service patients with a migraine or headache diagnosis were selected from the MEDSTAT MarketScan databases. Enrollment, medical claims, and prescriptions were analyzed from January 1, 1998 through June 30, 2000. Demographics, utilization, and evidence of seven comorbidities were calculated over a baseline period of 12 months before migraine diagnosis. Costs for patients taking triptan monotherapy during the 12 months after diagnosis were compared to those for patients taking other drug therapies (butalbitals, ergotamines, methysergide, midrin, oral narcotics, and stadol) over the same follow-up period. Ordinary least squares regressions of log healthcare expenditures controlled for demographics, utilization, and comorbidities at baseline. Smearing estimates were used to predict the marginal effect of drug treatment on annual healthcare expenditures. RESULTS: The final sample included 929 patients taking triptan monotherapy and 3,588 patients taking other drug therapies. Triptan patients were more likely to be female than other patients (83.2% vs. 73.5%, p < .001) and less likely to have at least one comorbidity (51% vs. 56%, p=.006) or to visit an emergency room (25% vs. 61%, p < .001); they also had fewer outpatient visits (5.2 vs.7.5, p < .001). Triptan patients had higher predicted costs from migraine-related visits and prescriptions ($4035.88 vs. $450.20, p < .0001), but lower predicted total expenditures ($7468.69 vs. $8974.03, p < .0001), even after controlling for patient differences. CONCLUSIONS: Triptan monotherapy was associated with lower total healthcare expenditures than were other migraine drug therapies, even though migraine-related costs for triptan patients were higher. The difference was over and above the cost influence of health status as measured by comorbidities and prior utilization.