The purpose of this study was to compare objective and self-reported outcomes of two treatments for managing mild, moderate, and severe obstructive sleep apnea (OSA) in adults: a mandibular advancement device (MAD) and continuous positive airway pressure (CPAP). Patients diagnosed with OSA by means of polysomnography (PSG) included one group treated with a custom-made, two-piece, adjustable MAD and a second group treated with CPAP for 8weeks. Before the initiation of the treatment, all patients assigned to MAD underwent drug-induced sleep endoscopy (DISE), and all CPAP group patients underwent manual titration of CPAP after PSG. Objective (PSG) and self-reported (Epworth Sleepiness Scale [ESS] and Short Form Health Survey [SF-36]) data were used to assess outcomes. Collected data includedapnea-hypopnea index (AHI), mean capillary oxygen saturation (SpO2), oxygen desaturation index (ODI), arousal index (AI), degree of daytime sleepiness, and quality of life. A PSG follow-up after 8weeks with MAD in situ, and data from the CPAP data card were used to assess the effect of the two treatments. A total of 59 patients included 30 treated with MAD and 29 treated with CPAP.Between baseline and the 8-week follow-up, the mean AHI score decreased significantly from 35.1 to 6.8 episodes/h (p < 0.001) in patients treated with MAD and from 35.2 to 3.0 episodes/h (p < 0.001) in patients treated with CPAP. The mean AHI score at the 8-week follow-up was significantly lower in CPAP group than in MAD group (p = 0.003). The two groups did not differ significantly at follow-up regarding SpO2 (p = 0.571), ODI (p = 0.273), AI (p = 0.100), ESS score (p = 0.648), and SF-36 score (p = 0.237). In the short term, patients on CPAP attained better PSG outcomes in terms of AHI reduction. Both MAD after DISE evaluation and CPAP resulted in similar improvements in clinical symptoms and health-related quality of life, even in patients with severe OSA.