Upper Airway Stimulation (UAS) of the hypoglossal nerve is a rapidly growing management option for patients with obstructive sleep apnea (OSA). Our study compares the treatment efficacy of UAS between those who were initially ineligible for UAS but subsequently met eligibility after multilevel surgery versus those who underwent isolated UAS for the treatment of moderate to severe OSA. The investigators implemented a retrospective single-center cohort study of patients aged 18+ years who presented for surgical evaluation of OSA from 2016-2019 and underwent UAS implantation. The predictor variable was eligibility status for UAS. Initially ineligible subjects were defined as having an apnea-hypopnea (AHI) > 65 events/hr, body mass index (BMI) > 32kg/m2, or complete concentric collapse (CCC) on drug-induced sleep endoscopy. Eligible subjects were defined as having an AHI between 15 and 65, with no CCC on drug-induced sleep endoscopy. The primary outcome was change in AHI which was measured preoperatively and 6months post UAS implantation. Secondary outcomes were change in Epworth sleepiness scale and Fatigue severity scale. Covariates were age, sex, and BMI. Data analysis involved descriptive statistics and multivariable statistical models; P<.05 was considered significant. Thirty six patients underwent UAS implantation from 2016-2019. Eighteen patients who were initially ineligible for UAS underwent multilevel surgery, including uvulopalatopharyngoplasty, distraction osteogenesis maxillary expansion, or maxillomandibular advancement. Mean age was 62.4±9years and BMI of 29.1±4kg/m2 with 5 female patients. The cohort of 17 patients who met criteria for UAS from the start had a mean age of 62.9±14years and mean BMI of 26.7±4kg/m2 with 2 female patients. Mean AHI reduction for the multilevel group was 37.6±21.2 events per hour (P<.001). Mean AHI reduction for the UAS-only group was 31.5±13 events per hour (P<.001). When adjusted for age, BMI, and sex, the multilevel group had a more significant reduction (18 AHI events) compared to the isolated group (P<.001). For patients who are ineligible for UAS due to severity of OSA or CCC of the velum, multilevel surgery including maxillomandibular advancement followed by UAS confers effective post-treatment results, which was superior to the UAS-only group.