OBJECTIVES: Migraine is one of the most prevalent neurological disorders in Europe, severely affecting ability to work and quality of life. Medical therapies are considered to be the “gold standard” of treatment. This study addresses osteopathic treatment for acute therapy or prophylactic therapy as an alternative to traditional therapies. DESIGN: Forty-two (42) female patients with migraine were randomized into an intervention group (n = 21) and a control group (n = 21). Outcomes were evaluated with three questionnaires before the treatment (t1) and 6 months later (t2). INTERVENTIONS: The intervention group received five 50-minute osteopathic manipulative treatments (OMT) over a 10-week period. The control group did not receive OMT, sham treatment, or physical therapy. Patients of this group only filled the questionnaires. Both groups continued with previously prescribed medication. METHODS: The Migraine Disability Assessment (MIDAS) and Short Form-36 (SF-36) questionnaires as well as a German “pain questionnaire” were used to assess pain intensity, the impact of migraine on daily life and health-related quality of life (HRQoL), and the number of days subjects suffered from migraine. RESULTS: Three (3) of the eight HRQoL domains of the SF-36 form in the intervention group showed significant improvement (from t1 to t2), with a general betterment exhibited in the other domains. The total MIDAS score, pain intensity, and disturbance in occupation due to migraine as well as number of days of disablements were also significantly reduced. The control group showed insignificant differences in these areas. CONCLUSIONS: This study affirms the effects of OMT on migraine headache in regard to decreased pain intensity and the reduction of number of days with migraine as well as working disability, and partly on improvement of HRQoL. Future studies with a larger sample size should reproduce the results with a control group receiving placebo treatment in a long-term follow-up.