INTRODUCTION: This systematic review provides supporting evidence for the accompanying clinical practice guideline on the referral of adults with obstructive sleep apnea (OSA) for surgical consultation. METHODS: The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies that compared the use of upper airway sleep apnea surgery or bariatric surgery to no treatment as well as studies that reported on patient-important and physiologic outcomes pre- and postoperatively. Statistical analyses were performed to determine the clinical significance of using surgery to treat obstructive sleep apnea in adults. Finally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was used to assess the evidence for making recommendations. RESULTS: The literature search resulted in 274 studies that provided data suitable for statistical analyses. The analyses demonstrated that surgery as a rescue therapy results in a clinically significant reduction in excessive sleepiness, snoring, blood pressure (BP), apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxygen desaturation index (ODI); an increase in lowest oxygen saturation (LSAT) and sleep quality; and an improvement in quality of life in adults with OSA who are intolerant or unaccepting of positive airway pressure (PAP) therapy. The analyses demonstrated that surgery as an adjunctive therapy results in a clinically significant reduction in optimal PAP pressure and improvement in PAP adherence in adults with OSA who are intolerant or unaccepting of PAP due to side effects associated with high pressure requirements. The analyses also demonstrated that surgery as an initial treatment results in a clinically significant reduction in AHI/RDI, sleepiness, snoring, BP, and ODI and an increase in LSAT in adults with OSA and major anatomical obstruction. Analysis of bariatric surgery data showed a clinically significant reduction in BP, AHI/RDI, sleepiness, snoring, optimal PAP level, BMI, and ODI and an increase in LSAT in adults with OSA and obesity. Analyses of very limited evidence suggested that upper airway surgery does not result in a clinically significant increase in risk of serious persistent adverse events and suggested that bariatric surgery may result in a clinically significant risk of iron malabsorption that may be managed with iron supplements. The task force provided a detailed summary of the evidence along with the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations. CITATION: Kent D, Stanley J, Aurora RN, et al. Referral of adults with obstructive sleep apnea for surgical consultation: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2021;17(12):2507-2531.