Purpose: The effectiveness of an appliance for the treatment of obstructive sleep apnea (OSA) shows inordinate interindividual differences. Also, its therapeutic effects still remain unresolved. This study examined and compared the effects of a mandibular advancement splint (MAS) on the masseter and submental muscles of patients with mild and moderate OSA. Materials and Methods: Twenty OSA patients (10 mild and 10 moderate) who refused or did not tolerate nasal continuous positive airway pressure were randomly selected among individuals whose apnea-hypopnea indices (AHIs) were determined at the sleep laboratory of the Department of Chest Diseases, Ege University, before the study. Two polysomnography (PSG) sessions were performed and evaluated: the first without an MAS for the first half of the night to determine baseline muscle activity and the second with an MAS for the other half of the night to follow the condition of muscle activity. Electromyograms (EMGs) of the sum of the submental musculature and masseter muscle were measured with PSGs. The highest EMG amplitudes of the muscles and their AHIs were recorded before and after use of the appliance. Data were analyzed statistically using a t test. Results: After insertion of the MAS device, EMG amplitudes increased significantly in the submental (P < .05) and masseter muscles (P < .05) of both mild and moderate OSA patients. However, the increase in muscle activity in the mild OSA group was significantly different from the moderate OSA group (P < .05). Accordingly, the mean EMG amplitude during moderate apnea episodes was lower than mild both with and without the appliance. After insertion of the MAS, the mean AHI in both mild and moderate OSA patients decreased significantly from baseline recordings (P < .05). Patients reported a favorable sleeping pattern and no dislodgement of the appliance during sleep. Conclusion: The MAS activated the masseter and submental muscles during sleep and prevented the upper airway from collapsing. The prosthetic appliance was useful in the treatment of both mild and moderate OSA syndrome. Int J Prosthodont 2009; 22: 586-593.