The mandibular advancement device (MAD) is a therapeutic option for obstructive sleep apnea syndrome (OSAS); however, for severe cases, it has a lower efficacy compared to continuous positive airway pressure (CPAP). This report aimed to present the efficacy of MAD in a patient with severe OSAS who refused CPAP. Video-polysomnography and polygraphy were performed before and after treatment, respectively. Three months after fitting and titrating the MAD, the apnea–hypopnea index was reduced from 56.2 events/h to 1.3 events/h and the minimum oxyhemoglobin saturation increased from 80% to 91%. Snoring time reduced from 75.2% to 0.2%. Our patient presented with low body fat, retrognathia, pharyngeal obstruction mainly along the anteroposterior axis and at the base of the tongue, and the ability to make wide protrusive movements with the jaw. In our opinion, these features could constitute a phenotype that may predict a positive response to MAD treatment even in severe cases of OSAS.