Abstract Objectives Fibromyalgia (FM) is a chronic pain syndrome characterized by a large variety of symptoms. Evidence suggests that an alteration of central nervous system processing of pain could be involved. The purpose of this study is to analyze clinical records of patients affected by FM who underwent osteopathic manipulative treatment (OMT), predominantly based on a myofascial release approach (MFR). Methods This retrospective study considered records of 21 FM patients with moderate or severe functional impact, who consented to OMT in addition to their usual care. The assessment considered the following measures: FIQ (functional status), SF36 (quality of life), VAS (pain), TSK (kinesiophobia) and PSQI (quality of sleeping). Patients were preliminarily assessed over a 1 month run-in phase, then after 1, 2 and 4 months; a 1 month follow-up was also considered. Results After one month, 71% of patients reported a decrease in functional impact and scores remained stable until follow-up (from 69.8 to 52.37, p≤0.001). Overall, after four months, patients improved their quality of life, with a score ranging from 33.47 to 42.6 (p≤0.05). We also observed a reduction of pain (p≤0.05). Conclusions A series of OMT sessions based on MFR could play a therapeutic role in improving functional status, pain and quality of life over a period of 4 months.