OBJECTIVE: To assess the effectiveness of OMT on chronic migraineurs using HIT-6 questionnaire, drug consumption, days of migraine, pain intensity and functional disability. DESIGN: 3-Armed randomized controlled trial setting: all patients admitted in the Department of Neurology of Ancona’s United Hospitals, Italy, with a diagnosis of migraine and without chronic illness, were considered eligible for the study. INTERVENTIONS: Patients were randomly divided into three groups: (1) OMT+medication therapy, (2) sham+medication therapy and (3) medication therapy only. Patients received 8 treatments in a study period of 6 months. MAIN OUTCOME MEASURES: Changing from baseline HIT-6 score. RESULTS: 105 subjects were included. At the end of the study, ANOVA showed that OMT significantly reduced HIT-6 score (mean change scores OMT-conventional care: -8.74; 95% confidence interval (CI) -12.96 to -4.52; p<0.001 and OMT-sham: -6.62; 95% CI -10.85 to -2.41; p<0.001), drug consumption (OMT-sham: RR=0.22, 95% CI 0.11-0.40; OMT-control: RR=0.20, 95% CI 0.10-0.36), days of migraine (OMT-conventional care: M=-21.06; 95% CI -23.19 to -18.92; p<0.001 and OMT-sham: -17.43; 95% CI -19.57 to -15.29; p<0.001), pain intensity (OMT-sham: RR=0.42, 95% CI 0.24-0.69; OMT-control: RR=0.31, 95% CI 0.19-0.49) and functional disability (p<0.001). CONCLUSIONS: These findings suggest that OMT may be considered a valid procedure for the management of migraineurs. The present trial was registered on www.ClinicalTrials.gov (identifier: NCT01851148).