Project Summary The overall objective of this randomized clinical trial is to test the effectiveness of a novel personalized approach to the surgical treatment of OSA in children with Down syndrome (DS). The estimated prevalence of obstructive sleep apnea (OSA) in children with Down syndrome (DS) ranges from 31-79%, compared to 1-5% in the general pediatric population. Adenotonsillectomy (AT) is the first line treatment for OSA in children, however, most studies of AT outcomes have excluded children with DS. Limited available evidence demonstrates that 50 to 90% of children with DS have persistent OSA after AT. Hypotonia and unfavorable craniofacial anatomy are commonly cited risk factors for failure of AT, however, there have been few attempts to characterize the pharyngeal anatomy or mechanisms of obstruction in this population. Drug-induced sleep endoscopy (DISE) enables direct observation of the sites and patterns of obstruction during sedated sleep using a flexible endoscope passed through the nose into the pharynx. Several small case series demonstrate that personalized DISE-directed surgery can be effective in treating OSA in children with DS. Because there have been few prospective studies and no randomized trials comparing different treatment options, there remains uncertainty about the most effective treatment for OSA in children with DS. It is our central hypothesis that a personalized DISE-directed surgical approach in children with DS will be superior to the recommended first line treatment of AT. To test this hypothesis, we propose an unprecedented randomized controlled trial of DISE-directed surgery vs AT in children with Down syndrome ages 2-18 years with the following specific aims: Aim 1: Compare the physiological outcomes of DISE-directed surgery vs AT in children with DS. Hypothesis 1: DISE-directed surgery will result in a greater improvement in the obstructive apnea-hypopnea index (OAHI) compared to the standard AT intervention after 6 months. Aim 2: Compare the clinical outcomes of DISE-directed surgery vs AT in children with DS. Hypothesis 2: DISE-directed surgery will result in a clinically significantly greater improvement in disease- specific QOL (OSA18) compared to the standard AT intervention after 6 months. This comparative effectiveness trial will be the first to directly compare a personalized surgical approach to the standard treatment in children with DS This novel approach may improve OSA outcomes and reduce the burden of unnecessary AT or secondary surgery for persistent OSA after an ineffective AT.