To evaluate whether mandibular advancement device therapy is recommended in patients affected by obstructive sleep apnea. In order to predict oral appliances therapy response, drug induced sleep endoscopy with cardio-respiratory polygraphy and mandibular advancement device simulator was carried out. Patients in which upper airway obstruction was resolved on all levels and AHI was normalized (< 5/h), were referred for oral appliance therapy. At 5 months follow up, a cardio-respiratory polygraphy with MAD was performed. 36 patients who have evidence of resolution of UA collapse and AHI below 5 events per hour, were referred for MAD therapy. At follow up, the mean AHI decreased from 29.1 ± 13.1 to 3.3/h ± 1.9 (p < 0.001). All the patients were responders. Combining the evaluation of drug induced sleep endoscopy and cardio-respiratory polygraphy data simultaneously during mandibular protrusion, has the potential to be a useful tool for prediction of MAD therapy response.