Context: Migraine headache is highly prevalent in the United States, resulting in large healthcare expenditures. Objective: To determine whether the use of osteopathic manipulative treatment (OMT) at an osteopathic family practice residency clinic affected the cost of treating patients with migraine headache, compared with non-OMT care at the osteopathic clinic and care at an allopathic family practice residency clinic. Methods: A retrospective review of electronic medical records from patients treated for migraine at two residency clinics within the Florida Hospital organization from July 1, 2002, to June 30, 2007. One of the clinics was osteopathic and offered OMT services, and the other clinic was allopathic and did not offer OMT. All costs compiled during the office visits and costs of prescribed medications were tabulated for each patient. Patients' pain-severity ratings, as reported in office visits in 2006 and 2007, were also tabulated. Results: Electronic medical records from 631 patients, representing 1427 migraine-related office visits, were analyzed. Average cost per patient visit was approximately 50% less at the osteopathic clinic than at the allopathic clinic ($195.63 vs $363.84, respectively; P<.001). This observed difference was entirely attributable to the difference in the average number of medications prescribed per visit at the two clinics, with 0.696 prescriptions at the osteopathic clinic and 1.285 prescriptions at the allopathic clinic (P<.001). This difference in prescription number resulted in a lower average medication cost per visit at the osteopathic clinic than at the allopathic clinic ($106.94 vs $284.93, respectively; P<.001). Patients at the osteopathic clinic were 5 years younger on average than at the allopathic clinic (P<.001). No statistically significant difference was observed between the two practices in patients' ratings of pain severity. Conclusion: The inclusion of OMT in a treatment regimen for patients with migraine headache may lower the cost of the treatment regimen. However, further study is needed to confirm these results.