The authors tested the hypothesis that obstructive sleep apnea (OSA) signs/symptoms are associated with the occurrence of temporomandibular disorder (TMD), using the OPPERA prospective cohort study of adults aged 18 to 44 years at enrollment (n = 2,604) and the OPPERA case-control study of chronic TMD (n = 1,716). In both the OPPERA cohort and case-control studies, TMD was examiner determined according to established research diagnostic criteria. People were considered to have high likelihood of OSA if they reported a history of sleep apnea or ≥ 2 hallmarks of OSA: loud snoring, daytime sleepiness, witnessed apnea, and hypertension. Cox proportional hazards regression estimated hazard ratios (HRs) and 95% confidence limits (CL) for first-onset TMD. Logistic regression estimated odds ratios (OR) and 95% CL for chronic TMD. In the cohort, 248 individuals developed first-onset TMD during the median 2.8-year follow-up. High likelihood of OSA was associated with greater incidence of first-onset TMD (adjusted HR = 1.73; 95% CL, 1.14, 2.62). In the case-control study, high likelihood of OSA was associated with higher odds of chronic TMD (adjusted OR = 3.63; 95% CL, 2.03, 6.52). Both studies supported a significant association of OSA symptoms and TMD, with prospective cohort evidence finding that OSA symptoms preceded first-onset TMD.