Obstructive sleep apnea (OSA) is a common disorder characterized by recurrent narrowing and closure of the upper airway, leading to intermittent oxygen desaturation and sympathetic activation. Moderate-to-severe OSA, defined by an apnea-hypopnea index (AHI) of 15 or more events per hour, is an independent risk factor for insulin resistance, dyslipidemia, vascular disease, and death. Continuous positive airway pressure (CPAP) is effective in reducing these risks, but its effectiveness is limited by poor patient adherence. Alternative treatments include oral appliances and upper-airway surgeries, but their efficacy is not consistently supported by evidence-based reviews. Upper-airway stimulation, which involves electrical stimulation of the hypoglossal nerve, has shown promise in feasibility trials. In this study, 126 patients with moderate-to-severe OSA who had difficulty with CPAP were enrolled. The primary outcomes were the AHI and oxygen desaturation index (ODI), with secondary outcomes including the Epworth Sleepiness Scale, the Functional Outcomes of Sleep Questionnaire (FOSQ), and oxygen saturation levels. At 12 months, the median AHI decreased by 68% from 29.3 to 9.0 events per hour, and the ODI decreased by 70% from 25.4 to 7.4 events per hour. Secondary outcomes showed significant improvements in sleepiness and quality of life. In a randomized therapy-withdrawal trial, patients who continued therapy had significantly lower AHI scores compared to those who had their device turned off. The rate of serious adverse events was less than 2%. The study demonstrated that upper-airway stimulation significantly improved the severity of OSA and subjective measures of sleepiness and quality of life. The results suggest that this therapy is a viable alternative for patients who cannot tolerate CPAP. The study was funded by Inspire Medical Systems and conducted at multiple centers. The findings indicate that upper-airway stimulation is a safe and effective treatment for moderate-to-severe OSA.Obstructive sleep apnea (OSA) is a common disorder characterized by recurrent narrowing and closure of the upper airway, leading to intermittent oxygen desaturation and sympathetic activation. Moderate-to-severe OSA, defined by an apnea-hypopnea index (AHI) of 15 or more events per hour, is an independent risk factor for insulin resistance, dyslipidemia, vascular disease, and death. Continuous positive airway pressure (CPAP) is effective in reducing these risks, but its effectiveness is limited by poor patient adherence. Alternative treatments include oral appliances and upper-airway surgeries, but their efficacy is not consistently supported by evidence-based reviews. Upper-airway stimulation, which involves electrical stimulation of the hypoglossal nerve, has shown promise in feasibility trials. In this study, 126 patients with moderate-to-severe OSA who had difficulty with CPAP were enrolled. The primary outcomes were the AHI and oxygen desaturation index (ODI), with secondary outcomes including the Epworth Sleepiness Scale, the Functional Outcomes of Sleep Questionnaire (FOSQ), and oxygen saturation levels. At 12 months, the median AHI decreased by 68% from 29.3 to 9.0 events per hour, and the ODI decreased by 70% from 25.4 to 7.4 events per hour. Secondary outcomes showed significant improvements in sleepiness and quality of life. In a randomized therapy-withdrawal trial, patients who continued therapy had significantly lower AHI scores compared to those who had their device turned off. The rate of serious adverse events was less than 2%. The study demonstrated that upper-airway stimulation significantly improved the severity of OSA and subjective measures of sleepiness and quality of life. The results suggest that this therapy is a viable alternative for patients who cannot tolerate CPAP. The study was funded by Inspire Medical Systems and conducted at multiple centers. The findings indicate that upper-airway stimulation is a safe and effective treatment for moderate-to-severe OSA.