Aims: To conduct a systematic review with meta-analysis of randomized controlled trials (RCTs) that have assessed the efficacy of intraoral orthopedic appliances to reduce pain in patients with temporomandibular disorders affecting muscle and joint (TMJD) compared to subjects receiving placebo control, no treatment, or other treatments. Methods: A search strategy of MEDLINE, the Cochrane Library, the Cochrane CENTRAL Register, and manual search identified all English language publications of RCTs for intraoral appliance treatment of TMJD pain during the years of January 1966 to March 2006. Two additional studies from 2006 were added during the review process. Selection criteria included RCTs assessing the efficacy of hard and soft stabilization appliances, anterior positioning appliances, anterior bite appliances, and other appliance types for TMJD pain. Pain relief outcome measures were used in the meta-analyses, and the QUORUM criteria for data abstraction were used. A quality analysis of the methods of each RCT was conducted using the CONSORT criteria. The review findings were expressed both as a qualitative review and, where possible, as a mathematical synthesis using meta-analysis of results. Results: A total of 47 publications citing 44 RCTs with 2,218 subjects were included. Ten RCTs were included in two meta-analyses. In the first meta-analysis of seven studies with 385 patients, a hard stabilization appliance was found to improve TMJD pain compared to non-occluding appliance. The overall odds ratio (OR) of 2.46 was statistically significant (P = .001), with a 95% confidence interval of 1.56 to 3.67. In the second meta-analysis of three studies including 216 patients, a hard stabilization appliance was found to improve TMJD pain compared to no-treatment controls. The overall OR of 2.15 was positive but not statistically significant, with a 95% confidence interval of 0.80 to 5.75. The quality (0 to 1) of the studies was moderate, with a mean of 55% of quality criteria being met, suggesting some susceptibility to systematic bias may have existed. Conclusion: Hard stabilization appliances, when adjusted properly, have good evidence of modest efficacy in the treatment of TMJD pain compared to non-occluding appliances and no treatment. Other types of appliances, including soft stabilization appliances, anterior positioning appliances, and anterior bite appliances, have some RCT evidence of efficacy in reducing TMJD pain. However, the potential for adverse events with these appliances is higher and suggests the need for close monitoring in their use. Keywords: intraoral orthopedic appliances, systematic review, temporomandibular disorders