Aims: To investigate the effects of local intramuscular injection of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine on chronic myofascial pain and mandibular function in temporomandibular disorder patients. Methods: Fourteen myofascial temporomandibular disorder pain patients (10 women and 4 men) were recruited. The subjects completed 2 sessions in a double-blinded randomized and placebo-controlled trial. They received a single injection of 0.2 mL ketamine or placebo (buffered isotonic saline [NaCl], 155 mmol/L) into the most painful part of the masseter muscle. The primary outcome parameters were spontaneous pain assessed on an electronic visual analog scale and numeric rating scale. In addition, numeric rating scale of unpleasantness, numeric rating scale of pain relief, pressure pain threshold, pressure pain tolerance, completion of a McGill Pain Questionnaire and pain drawing areas, maximum voluntary bite force and maximum voluntary jaw opening were obtained. Paired t tests and analysis of variance were performed to compare the data. Results: There were no main effects of the treatment on the outcome parameters except for a significant effect of time for maximum voluntary bite force (analysis of variance; P = .030) and effects of treatment, time, and interactions between treatment and time for maximum voluntary jaw opening (analysis of variance; P .047). Conclusion: These results suggest that peripheral NMDA receptors do not play a major role in the pathophysiology of chronic myofascial temporomandibular disorder pain. Although there was a minor effect of ketamine on maximum voluntary jaw opening, local administration may not be promising treatment for these patients. Keywords: experimental pain, glutamate, ketamine, muscle pain, orofacial pain, temporomandibular disorders, trigeminal physiology