This prospective, cohort study evaluated the role of sleep nasendoscopy (SNE) with simultaneous mandibular protrusion in predicting successful mandibular advancement splint (MAS) therapy in subjects with obstructive sleep apnoea (OSA). Nineteen OSA subjects diagnosed by overnight polysomnography were referred for MAS therapy, following SNE investigation. A Herbst MAS was fabricated for each subject. Once this had been adjusted for maximal, subjective, therapeutic effect, follow-up sleep studies were undertaken with the appliance in situ. The SNE was repeated with the appliance in place to allow the effects of the original mandibular protrusion and the actual effect of the MAS to be compared. The MAS was removed and the original and current site(s) of obstruction evaluated. Pre-treatment SNE showed airway obstruction at the following levels: intermittent multi-level (16 subjects), sustained multi-level (two subjects) and tongue base (one subject). In all individuals, gentle advancement of the mandible during SNE improved airway patency and reduced snoring. When the SNE was repeated with the MAS in situ, all subjects showed improvements in snoring and airway patency. Follow-up sleep studies confirmed the efficacy of the MAS, with all patients showing a reduction in the apnoea/hypopnoea index (AHI). Median reductions in AHI (from 28.1 to 6.1, P < 0.001) and Epworth Sleepiness Scale (ESS) scores (from 9 to 6, P < 0.001) were highly statistically significant. The results suggest that SNE with concomitant mandibular advancement to mimic MAS wear, could be a valuable prognostic indicator of successful MAS treatment.