Background: Upper airway stimulation (UAS) is a treatment approach for patients with moderate-to-severe obstructive sleep apnea who cannot adhere to continuous positive airway pressure therapy. Objective: The objective was to evaluate added patient benefit and cost-effectiveness of UAS in the German health care system. Methods: We used a decision-analytic Markov model to project major adverse cardiovascular or cerebrovascular events (myocardial infarction [MI] or stroke), motor vehicle collision (MVC), mortality, quality-adjusted life years (QALYs), and costs. The assumed reduction in the apnea-hypopnea index with UAS compared to no treatment is based on German real-world data. Other input data were derived from the literature, public statistics, and multivariate regression. Cost-effectiveness was evaluated in Euros per QALY gained, both discounted at 3%. Results: UAS was projected to reduce event risks (10-year relative risk for stroke, MI, cardiovascular death, and MVC: 0.76, 0.64, 0.65, and 0.34, respectively), and to increase survival by 1.27 years. While the UAS strategy incurred an additional 1.02 QALYs within the patient lifetime, there were also additional costs of EUR 45,196, resulting in an incremental cost-effectiveness ratio of EUR 44,446 per QALY gained. -Conclusions: In the present model-based analysis, UAS therapy provides meaningful benefit to patient-relevant endpoints and is a cost-effective therapy in the German setting.