OBJECTIVES:: Headaches disorders are one of the most common neurological problems. Osteopathic manipulative therapy (OMTh) is considered by some practitioners to be useful for headache management, but there is limited scientific evidence regarding the effectiveness. This study aims to provide a systematic literature review to assess the effectiveness of OMTh in patients with headache. METHODS:: Electronic searches were conducted in Cochrane, Embase, LILACS, Cochrane Library, OSTMED.DR and PEDro databases until December 2016. Searches were conducted using the following terms: “Manipulation, Osteopathic” and “Headache”. No language limits were applied. Two independent reviewers extracted trial information and scored trials for methodological quality. A consensus method was used to resolve disagreements related to the assessment of studies methodological quality. RESULTS:: The systematic literature review resulted in 51 bibliographic references from PUBMED, 7 from LILACS, 295 from EMBASE, 28 from Cochrane Library, 11 from PEDro and 219 from OSTMED.DR. After reading the titles and abstracts, 597 references that did not meet the eligibility criteria and were duplicated, were excluded. Fourteen papers were selected for more detailed analysis. Then, five studies were considered in this review. All studies were randomized clinical trials and were assessed as having low risk of bias according to the Cochrane Collaboration criteria, although there was heterogeneity in the outcome measures and control interventions. The number of OMTh performed in the studies was from 3 to 8 treatments, and the follow-up time ranged from 6 weeks to 6 months. All studies reported improvements with OMTh compared to the sham therapy or standard care only, showing reduction of migraine episodes, medication use, pain and functional disability. CONCLUSIONS::  The present study provides evidence that OMTh may be beneficial in the treatment of patients with headache. However, caution is required in the interpretation of these findings due to the limited number of studies available and the small sample sizes.