To evaluate the short-term effectiveness of orthopedic manual therapy (OMT) in signs and symptoms of myofascial pain (MFP) in young adults. Materials and Methods: An experimental controlled clinical study was performed in young adults between 19 and 24 years old.Thirty-one patients with MFP according to Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) were divided into two groups. Group A: Orthopedic Manual Therapy (n=16; 10 females, 6 males; 21.6 ± 1.70 years old), and Group B: Control group (n=15; 10 females, 5 males; 20.9 ± 2.00 years old). The participants of group A were treated for a period of 6 weeks; Six therapeutic interventions were performed.Degree of dysfunction (Helkimo index), pain level (VAS scale), and range of mandibular movements (opening and lateral movements) were taken at baseline (T0) and immediately at post-treatment (T1). The data were analyzed with chi-square test and t-test; p<0.05 was considered significant. Result: After the OMT, there were no significant changes in diagnosis of MFP according to RDC/TMD (p=0.41); however, there was a statistically significant improvement in the Helkimo index (p=0.0083) and the level of pain according to the VAS scale (p=0.0004). Mandibular movements did not show significant differences (p>0.05). Conclusion: This study suggested that a 6-week period of OMT treatment has a clinically significant effect in pain level and degree of dysfunction in patients with MFP. A longer follow-up study is required to better assess the effects of manual therapy.