The aim of the present study was to evaluate the effects of hyperbaric oxygen (HBO) therapy on myofascial pain syndrome (MPS). Thirty patients with the diagnosis of MPS were divided into HBO (n=20) and control groups (n=10). Patients in the HBO group received a total of 10 HBO treatments in 2 weeks. Patients in the control group received placebo treatment in a hyperbaric chamber. Pain threshold and visual analogue scale (VAS) measurements were performed immediately before and after HBO therapy and 3 months thereafter. Additionally, Pain Disability Index (PDI) and Short Form 12 Health Survey (SF-12) evaluations were done before HBO and after 3 months. HBO therapy was well tolerated with no complications. In the HBO group, pain threshold significantly increased and VAS scores significantly decreased immediately after and 3 months after HBO therapy. PDI, Mental and Physical Health SF-12 scores improved significantly with HBO therapy after 3 months compared with pretreatment values. In the control group, pain thresholds, VAS score, and Mental Health SF-12 scores did not change with placebo treatment; however, significant improvement was observed in the Physical Health SF-12 test. We concluded that HBO therapy may be a valuable alternative to other methods in the management of MPS. Our results warrant further randomized, double-blinded and placebo-controlled studies to evaluate the possible role of HBO in the management of MPS.