Background: Hypoglossal nerve stimulation (HNS) is an emerging surgical treatment for select patients with obstructive sleep apnea (OSA). Although HNS has shown long-term effectiveness, 37% of patients do not fully respond to treatment. This study aims to determine if certain cephalometric variables are associated with treatment response following HNS. We hypothesize that patients with retrognathic phenotypes, as determined by bony cephalometric measurements on lateral neck X-ray, would have suboptimal benefit from HNS. Methods: A single-center retrospective cohort study of 43 patients who underwent HNS surgery from 2019 to 2022 was conducted. Skeletal cephalometric values were obtained using lateral neck X-rays. Pre/post-surgery Apnea Hypopnea Index (AHI) and subjective sleep quality measures were compared. Optimal clinical cut-off values (Youden Index (YI)) of significant cephalometric variables were calculated utilizing receiver operating curves (ROC) analyses. Response to surgery was defined as AHI < 20 with ≥50% reduction in AHI score. Univariate analyses included Wilcoxon Signed-Rank Test and Spearman’s Rho. Results: Most patients were male (62.9%) with a median age of 58.6 years and median BMI of 28.9. The median baseline AHI 29.7 improved to 6.4 (P < .001). Average O2 saturation, O2 nadir, and subjective sleep also improved. Twenty-six patients (72.2%) fully responded to surgery. Four cephalometric values were associated with less improvement: smaller SNA (YI 78.5°) and SNB (YI 80.5°) angles, shorter mandible length (YI 12.8 and 13.1 cm), and greater mandible-hyoid distance (YI 20.4 and 30.7 mm). Conclusions: Patients with retrusive facial skeletons were less likely to fully respond to HNS surgery and would likely benefit from evaluation for orthognathic surgery for treatment of their OSA. Cephalometric assessment and an appropriate referral to a maxillofacial surgeon should be considered in the initial surgical work-up for OSA to better guide treatment selection.