| Summary: | Patients with obstructive sleep apnea (OSA) that do not tolerate/accept continuous positive airway pressure (CPAP) are candidates for surgical alternatives. Hypoglossal nerve stimulation (HNS) through the implantation of the Inspire<sup>®</sup> device constitutes a minimally invasive operative option. The main objective of this study is to estimate, under real-world clinical practice conditions, the 3-month impact on the quality of life (IQoL) of the HNS in patients with moderate/severe OSA who do not tolerate or accept CPAP, compared to patients who did not receive HNS. As a baseline, the unadjusted EuroQol utility index was 0.764 (SD:0.190) in the intervention group (IGr) and 0.733 (SD:0.205) in the control group (CGr); three months later, the indexes were 0.935 (SD: 0.101) and 0.727 (SD:0.200), respectively. The positive impact on quality of life was estimated to be +0.177 (95% CI: 0.044–0.310; <i>p</i> = 0.010). All dimensions in the IGr improved compared to CGr, especially for usual activities (<i>p</i> < 0.001) and anxiety/depression (<i>p</i> > 0.001). At the end of the follow-up, there was no significant difference in the quality of life between the general Spanish population and the IGr (difference: 0.012; CI95%: −0.03 to −0.057; <i>p</i> = 0.0578) for the same age range; however, there was a difference concerning the CGr (difference: −0.196; CI95%: −0.257 to −0.135; <i>p</i> < 0.001). In conclusion, patients with moderate/severe OSA implanted with the Inspire<sup>®</sup> device showed a positive IQoL.
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