Objectives To evaluate the efficacy of mandibular advancement devices (MADs) in improving apnea-hypopnea index (AHI) in positional obstructive sleep apnea (POSA), compared with a control group of nonpositional OSA (NPOSA) patients, from mild to very severe degree, in order to to find the main variables characterizing the examined group as potential predictors of treatment success. Materials and Methods In the present observational study, we retrospectively collected polysomnographic records of 39 positional adult patients, divided into 30 supine isolated OSA (siOSA) and 9 supine predominant OSA (spOSA) undergoing MADs from 2003 to 2019, and compared with those of a control group of 47 NPOSA patients. Demographics and anthropometrical data, home sleep apnea test (HSAT) records, drug-induced sleep endoscopy (DISE) results, and dental casts evaluation were analyzed pre- and post-treatment with MADs. Results A prevalence of the male sex (86%), mean age of 49,4 ± 14.98 years, and mean body mass index (BMI) of 26.74 ± 4.29 kg/m 2 were found among the OSA patients with significant differences between the three groups for sex and BMI. After MADs, the HSAT revealed significant reduction of AHI in all of the groups, with greater reduction of the supine AHI in POSA and significant reduction of the snore index for NPOSA. The hypopharynx section (H) of the NOHL Index, a fourth degree of hypopharyngeal collapse and an anteroposterior pattern was the most frequent to occur (19.9%) from DISE exam. No significant correlation between the initial total AHI and the dental variables was found, except for a reduced maxillary intermolar distance. Conclusion MADs are effective in reducing AHI in POSA and NPOSA patients from mild to very severe degree. Supine AHI decreased after treatment with MADs mainly in siOSA and spOSA patients compared with the NPOSA group. The snore index decreased significantly after treatment with MADs in all groups, showing the greater reduction in the NPOSA group. The tongue base (H) represented the most frequent anatomic area of collapse and there was a high prevalence of upper maxillary constriction.