© 2019 The American Laryngological, Rhinological and Otological Society, Inc. Objective: Examine the patient characteristics of those undergoing upper airway stimulation (UAS) for the treatment of continuous positive airway pressure (CPAP)-refractive obstructive sleep apnea (OSA) at a tertiary care medical center to determine objective clinical predictors of success. Methods: Retrospective chart review of the first 25 consecutive patients between August 2015 and December 2016 treated with UAS at a tertiary care academic center. Demographic data, medical and sleep history, pre- and postoperative polysomnography data, and sleep endoscopy findings were collected. Statistical analysis was performed using two-sided t test with bivariate and linear regression analysis. Results: In our cohort of 25 patients, mean age was 67.5 ± 7.6 years, and mean body mass index (BMI) was 28.2 ± 3.8 kg/m2 with 42% female. One patient was excluded from analysis for unmasking of complete central apnea with therapy. AHI decreased by a mean of 33.8 events/hour following treatment (95% confidence interval: 25.8 to 41.7, P < 0.001). Preintervention AHI was associated with therapy response, with each point of preintervention AHI leading to an average decrease of 1.03 points (P < 0.001). Eighty-three percent of patients achieved a treatment AHI < 5, whereas 92% achieved an AHI < 10. Mean device use was 49.5 ± 10.4 hours per week. Ninety-two percent of patients were discharged the day of surgery. No major adverse events occurred. Conclusion: UAS continues to gain popularity for the treatment of CPAP-refractive OSA; therefore, identification of predictors of success is crucial. Our study, although small, suggests that more severe preintervention AHI does not preclude significant therapy response and may expand the inclusion criteria for UAS, meriting further investigation. Level of Evidence: 4 Laryngoscope, 130:556–560, 2020.