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Patients with obstructive sleep apnoea (OSA) in long-term treatment with a mandibular advancement device (MAD) to increase the upper airway space may develop changes in the temporomandibular joint (TMJ) and the oro-facial function due to the protruded jaw position during sleep. The aim was to investigate the influence of long-term MAD treatment on the TMJs, oro-facial function and occlusion. This prospective study included 30 men and 13 women (median age 54) with OSA [Apnoea-Hypopnoea Index (AHI): 7-57]. They were examined with the Nordic Orofacial Test Screening (NOT-S), the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and cone beam computed tomography (CBCT) of the TMJs. The examination was performed before MAD treatment (T0), and 3-6 months (T1, no CBCT), 1 year (T2) and 3 years (T3) after treatment start. The results were analysed as long term (T0-T3, n = 14) and short term (T0-T2, n = 24) by t-test, Fisher's exact test and anova. Both long- and short-term analyses revealed a reduction in AHI (P < 0·002). Significant long term were increased scores in the NOT-S Interview (P < 0·045), reduced vertical overbite (P < 0·031) and increased jaw protrusive movement (P < 0·027). TMJ changes were found as joint sounds in terms of reciprocal clicking and crepitus, short term as a decrease and subsequent recurrence (P < 0·053; P < 0·037). No significant radiological changes were found. In conclusion, MAD treatment is beneficial to some OSA patients, but might induce changes in the TMJs, the oro-facial function and the occlusion. However, these changes seemed to be less harmful than previously reported with careful adaptation, control and follow-ups.