This article presents a patient experiencing several years of pain associated with bilateral failed temporomandibular joint (TMJ) Proplast/Teflon fossa prostheses. Despite surgical removal of the prostheses and comprehensive conservative management, including typical pharmacotherapy approaches for chronic pain, pain was still not relieved, and management was revised to target a putative chronic inflammatory disorder. Methotrexate was prescribed because of its known efficacy for inflammation and pain reduction in rheumatoid arthritis. Titration of methotrexate dosage over 5 months to a weekly dose of 20 mg resulted in reduced pain intensity at rest, increased pain-free maximal jaw opening, and a reduction in the sensory component of the McGill Pain Questionnaire. Maximum assisted jaw opening remained the same, as did the palpation tenderness of both TMJs and of the masseter and temporalis muscles. Methotrexate pharmacotherapy may represent a viable option when conservative treatments have failed to provide significant pain relief in patients who have had Proplast/Teflon TMJ implants.