BackgroundFew data are available comparing first-line positive airway pressure (PAP) therapy of obstructive sleep apnea (OSA), especially auto-adjusting PAP (aPAP), with second-line hypoglossal nerve stimulation (HGNS) therapy. The aim of this study was to directly compare these therapeutic options by standard polysomnography (PSG)-related parameters and patient-reported outcomes in comparable groups. Methods20 patients (aged 57.30 ± 8.56 years; 6 female) were included in the HGNS and 35 patients (aged 56.83 ± 9.20 years; 9 female) were included in the aPAP group. In both groups participants had to fit the current guideline criteria for HGNS treatment. Groups were compared by analysis of covariance (ANCOVA) using inverse propensity score weighting. ResultsPropensity scores did not differ between groups. Pre-therapeutic AHI (HGNS: 40.22 ± 12.78/h; aPAP: 39.23 ± 12.33/h) and ODI (HGNS: 37.9 ± 14.7/h, aPAP: 34.58 ± 14.74/h) were comparable between the groups. After 413.6 ± 116.66 days (HGNS) and 162.09 ± 140.58 days (aPAP) of treatment AHI (HGNS: 30.22 ± 17.65/h, aPAP group: 4.71 ± 3.42/h; p < 0.001) was significantly higher in the HGNS group compared to the aPAP group. However, epworth sleepiness scale (ESS) was post-interventionally significantly lower in the HGNS group compared to the aPAP group (pretherapeutic: HGNS: 13.32 ± 5.81 points, aPAP: 9.09 ± 4.71 points; posttherapeutic: HGNS: 7.17 ± 5.06 points; aPAP: 8.38 ± 5.41 points; p < 0.01). ConclusionThese are novel real-world data. More research on the key parameters regarding titration of the HGNS neurostimulation parameter tuning and on the impact of factors influencing HGNS adherence is needed.