PURPOSE: To determine the effectiveness of laser therapy for managing patients with orofacial pain (OFP). In addition, to determine which parameters provide the best treatment effects to reduce pain, improve function, and quality of life in adults with OFP. METHODS: Systematic review. Searches were conducted in six databases; no date or language restrictions were applied. Studies involving adults with OFP treated with laser therapy were included. The risk of bias (RoB) was performed with the Revised Cochrane RoB-2. A meta-analysis was structured around the OFP type, and outcomes. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessed the overall certainty of the evidence. RESULTS: Eighty-nine studies were included. Most studies (n = 72, 80.9%) were considered to have a high RoB. The results showed that laser therapy was better than placebo in improving pain, maximal mouth open (MMO), protrusion, and tenderness at the final assessment, but with a low or moderate level of evidence. The best lasers and parameters to reduce pain are diode or gallium-aluminum-arsenide (GaAlAs) lasers, a wavelength of 400-800 or 800-1500 nm, and dosage of <25 J/cm2. CONCLUSIONS: Laser therapy was better than placebo to improve pain, MMO, protrusion, and tenderness. Also, it was better than occlusal splint to improve pain, but not better than TENS and medication.Implications for rehabilitationLaser therapy was found to be good in improving pain, maximal mouth opening, jaw protrusion, and tenderness at the end of the treatment.For patients with all types of temporomandibular disorders (TMDs) (myogenous, arthrogenous, and mixed), the following lasers and parameters are recommended: diode or gallium-aluminum-arsenide (GaAlAs) laser, wavelength of 400-800 or 800-1500 nm, and a dosage <25 J/cm2.For patients with arthrogenous TMDs, the following lasers and parameters are recommended: Diode laser and a wavelength between 400 and 800 nm.For patients with myogenous TMDs, the following lasers and parameters are recommended: diode laser, wavelength between 800 and 1500 nm, and dosage of <25 J/cm2.For patients with mixed TMDs, the following lasers and parameters are recommended: diode, GaAlAs, or infrared laser, a wavelength of 800-1500 nm, a dosage >100 J/cm2, and an application time between 15 and 30 s or >60 seconds.