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Obstructive sleep apnea (OSA) is the most common respiratory disease in the developed world and is commonly treated with positive airway pressure therapy (PAP). Recently, hypoglossal nerve (HNS) has been introduced as alternative treatment for OSA patients with PAP intolerance. We report the initial results with HNS treatment from Spain. Patients with OSA and PAP intolerance were screened for HNS treatment with the Inspire™ system. After implantation and activation, efficacy was evaluated with polysomnography and indication-specific questionnaires. Adherence data was recorded from the stimulation system. 18 patients (51.83 ± 11.64 years, 94% male, mean Body Mass Index 27.94 ± 3.20) received an Inspire™ UAS system and were included for analysis. Mean procedure time was 202.83 ± 64.87 min. and average hospital stay 26.67 ± 7.54 h. Mean Apnea–Hypopnea-Index was reduced by 63.44% (p ≤ 0.0001), while daytime sleepiness improved to a mean ESS score of 6.60 ± 1.25 (p ≤ 0.0001 Therapy response (AHI reduction > 50% and final AHI < 20), was reached in 64.70 and normalization of daytime sleepiness (final ESS score < 10) in 100% of patients. Therapy adherence was 6.32 ± 1.71 h per night. HNS is a safe and leads to effective OSA control and symptom normalization in selected OSA patients with PAP intolerance. Stimulation therapy is well accepted, as demonstrated by high adherence. Implementation of HNS therapy into an OSA program in Spain is feasible with acceptable learning curve and moderate resource utilization. [ABSTRACT FROM AUTHOR]