Oral appliances (OA) are the recommended first-line option for mild-to-moderate obstructive sleep apnea (OSA)-hypopnea. However, there is a lack of evidence to compare the effectiveness of OA in different severities of OSA. The purpose of this study was to investigate the therapeutic effects of preferred OA (tongue retention devices [TRD] and mandibular advancement device [MAD]) in different severities of OSA.PubMed/MEDLINE, The Cochrane Library, and Web of Science.Concentrating on the efficacy of OA, 2 authors searched 3 databases up to November 10, 2022, independently and systematically, following the requirements and steps of the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.Ultimately, 42 studies with 2265 patients met the criteria for inclusion in OA. Overall, the apnea-hypopnea index improved by 48% (5.6), 67% (14.92), and 62% (32.1) in mild, moderate, and severe OSA, respectively. Subgroup analysis showed a significant difference between MAD and TRD efficacy in mild OSA (58% vs 21%). However, no significant difference was seen between MAD and TRD efficacy in moderate (67% vs 66%) and severe OSA (66% vs 51%). There was no significant difference across groups in the Epworth Sleepiness Scale, oxygen desaturation index (ODI), and lowest oxygen saturation (LSAT).Overall, both TRD and MAD are effective treatments for moderate and severe OSA. MAD is efficacious in mild OSA, while TRD requires further validation. Furthermore, mild-moderate and severe OSA received similar improvements in sleepiness, ODI, and LSAT. This study complements the evidence for the efficacy of OA.© 2024 American Academy of Otolaryngology-Head and Neck Surgery Foundation.