The characteristics of non-obese patients with mild to moderate Obstructive Sleep Apnea Syndrome (OSAS) who will present with a good response to Mandibular Repositioning Appliance (MRA) treatment have not yet been well established in the literature. The aim of this study is to assess whether polysomnographic (PSG), demographic, anthropometric, cephalometric, and otorhinolaryngological parameters predict MRA success in the treatment of OSAS. Forty (40) males with mild and moderate OSAS were assessed pretreatment and 2-months post-treatment after wearing an MRA. Demographic, anthropometric, otorhinolaryngological (ENT), cephalometric, and polysomnographic parameters, including continuous positive airway pressure (CPAP) titrated pressure, dental models, Epworth Sleepiness Scale, quality of life (Short Form SF-36), and mood state (Profile of Mood States -POMS), were assessed. The responders exhibited fewer oropharyngeal alterations, increased upper pharyngeal space, reduced lower airway space, and increased mandibular intercanine width, and they had milder disease. Nevertheless, no predictive factors of MRA success could be found. MRA was more successful among men with a more pervious airway, a larger interdental width and milder OSAS. However, a combined [1] functional and structural assessment is needed to successfully predict the [2] effectiveness of MRA treatment of OSA.