Obstructive sleep apnea (OSA) is a highly prevalent sleep breathing disorder characterized by the collapse of the pharyngeal walls that entails recurrent episodes of cessation of breathing or decrease in airflow while sleeping. This results in sleep fragmentation, decreased oxygen saturation and an increase in the partial pressure of carbon dioxide, causing excessive daytime sleepiness, hypertension and increased prevalence of cardiovascular morbidity and mortality. Mandibular advancement devices (MAD) represent a valid alternative therapy to Continuous Positive Airway Pressure, thrusting the mandible forward, increasing the lateral diameter of the pharynx and reducing the collapsibility of the airway. Several investigations have focused on the detection of the best mandibular advancement amount in terms of effectiveness and tolerance, but few and contrasting data are available on the role of occlusal bite raise in reducing the apnea/hypopnea index (AHI). The aim of this systematic review with meta-regression analysis was to investigate the effect of the bite raise of MAD on AHI values in adult patients affected by OSA. An electronic search was performed in MEDLINE, the Cochrane Database, Scopus, Web of Science and LILACS. Randomized controlled trials (RCT) investigating the effectiveness of MAD in OSA patients were included. The quality of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and the risk of bias with the Cochrane risk-of-bias tool for randomized trials (RoB2). Six RCT were included. The success rate of each study was computed: (mean baseline AHI − mean post treatment AHI)/mean baseline AHI. The GRADE scores indicated that the quality of evidence was very low. The meta-regression analysis showed that there was no correlation between the occlusal bite raise and the AHI improvement.