Objective: Multiple temporomandibular joint (TMJ) surgeries with implants has been indicated as a contributing factor to chronic post-surgical pain. This prospective cohort study was conducted to assess the contribution of co-morbid conditions and temporomandibular joint (TMJ) surgery on the aggravation of temporomandibular disorders (TMD). Method: Subjects' data were obtained from the National Institute of Dental and Craniofacial Research TMJ Implant Registry and Repository (NIDCR's TIRR). Only patients with TMJ Disorders who received surgery, with or without implants, were included in this study. Patients completed a questionnaire at baseline assessing the characteristics of their complaint, co-morbid conditions, and demographics. At follow-up they completed a questionnaire asking “How has the problem changed in the past month?” The answer choices were: “It's gone; much improved; somewhat improved; same; worse and much worse. Patients were classified with aggravation if they answered worse or much worse. Unconditional logistic regression was performed to assess the contribution of co-morbid conditions or implant on the aggravation of TMD. Results: Two hundred eighty five patients completed the follow-up. From those, 148 patients received implant and 137 received another surgery. Patients who received implants presented severe pain characteristics in comparison to patients that received surgery without implants. In a multivariable logistic regression analysis, adjusting for all covariates, implant (OR: 2.29, 95%CI: 1.06 to 4.93, P = 0.04) was associated with TMJ aggravation at follow-up. Baseline muscle pain rheumatism (OR: 2.41, 95%CI: 1.11 to 5.26, P = 0.03), fibromyalgia (OR: 3.03, 95%CI: 1.26 to 7.28, P = 0.02), pain characteristics (OR: 1.26, 95%CI: 1.08 to 1.47, P = 0.004) were also related to TMD aggravation at follow-up. Conclusion: These results indicate that co-morbid conditions and implant may play a role in the aggravation of TMD, independent of pain severity. This study was funded by NIH/NIDCR grants # RO1DE11252 and # DE09737-09.