Objectives: This study is aimed to evaluate if the osteopathic manipulative treatment (OMT) is effective in patients with primary dysmenorrhea (PD). Methods: Randomized single-blinded controlled trial with OMT group and lighttouch treatment (LTT) group. Recruited women were 18-40 years (mean age 27 years), with regular menstrual cycle, normal body mass index (BMI), and a medical diagnosis of PD. Intervention: Patients received five OMT or five LTT over a menstrual cycle. The primary outcomes were average menstrual pain assessed by the numeric rating scale (NRS), the duration of pain, and quality of life (QoL) assessed by the SF-12 Short Form Health Survey and Patient Global Impression Change (PGIC). The secondary outcomes were NSAIDs intake, hours of absence from school/work, and menstrual-related symptoms. Results: 31 subjects were enrolled, of which five were excluded and the remaining 26 were randomized. Patients in OMT group had significant improvement in every outcome, including the average menstrual pain that decreased from 5.35 ± 0.28 to 1.98 ± 0.24 (-63.0%; p<0.001). The mean SF-12 physical component score (PCS) improved from 31.35 ± 1.70 to 49.56 ± 1.92 (+58.1%, p<0.001), the mean SF-12 mental component score (MCS) improved from 38.36 ± 1.16 to 52.04 ± 0.94 (+35.7%; p<0.001). LTT group showed no improvements. Conclusion: OMT was effective in reducing menstrual pain and improving Quality of Life of dysmenorrheic women.