Introduction: Myofascial pain dysfunction syndrome (MPDS) is a common temporomandibular joint disorder. Due to its multifactorial etiology, treatment usually involves more than one modality to obtain complementary results. The purpose of this study was to compare the combined effect of a low-level laser, a hard occlusal appliance, and conventional pharmacotherapy with pharmacotherapy only in the management of patients with MPDS. Methods: In this study, 15 patients with MPDS were diagnosed and randomly assigned to 3 groups (n=5). Subjects in Group 1 were treated with pharmacotherapy (PT); Group 2 received the diode laser (940 nm gallium arsenide) every other day for a total of 10 sessions, plus pharmacotherapy (PTL) and Group 3 were given hard occlusal splint 12 h/day for 4 weeks, plus pharmacotherapy (PTO). The intensity of pain was measured using the visual analog scale (VAS) prior to the treatment, 2 and 4 weeks after the onset of treatment and 2 weeks later. The maximum painless mouth opening and pain intensity at muscle palpation were also recorded. Comparisons were made between the groups via repeated measure analysis of variance (ANOVA) (P<0.05). Results: Pain relief in the subjective VAS was observed in both laser and appliance groups in the third and fourth examination sessions (P<0.05). No statistically significant reduction in pain was noted using pharmacotherapy only. The maximum painless mouth opening and muscle tenderness were not significantly different between the 3 groups (P>0.05). Conclusion: Both the laser and the occlusal appliance combined with pharmacotherapy proved to be effective for pain reduction in patients with MPDS. All groups, however, failed to result in a significant improvement in the maximum mouth opening or tenderness in masticatory muscles.