The efficacy of hypoglossal nerve stimulation (HGNS) therapy is limited by obstruction of the oropharyngeal lateral walls (OLWs). Our objective was to investigate the effect of palatine tonsillectomy on HGNS efficacy in obstructive sleep apnea (OSA)patients with OLW collapse. Case-control study of patients with moderate-to-severe OSA, complete-or-partial OLW collapse, and small tonsils (1 - 2+). Concomitant palatine tonsillectomy and HGNS (HGNS+T) were compared against a control group of patients who underwent HGNS alone. Single academic institution. Study outcomes were measures of HGNS efficacy defined asa %reduction in apnea-hypopnea index (AHI) (primary) and successful treatment response (50% AHI reduction to <15/h, logistic regression), respectively. Regression analyses quantified the additional effect of tonsillectomy (HGNS+T vsHGNS alone, independent variable) on HGNS efficacy. Analyses were adjusted for OLW collapse severity (complete vspartial), tonsil size, age, sex, body mass index, and baseline AHI. Nineteen patients underwent HGNS+T and had follow-up sleep testing for the current analysis. The control group (HGNS alone) consisted of 78 patients. Baseline demographics and OSA severity were similar between the groups, except HGNS+T group had increased prevalence of complete OLW collapse. Linear regression demonstrated that adding tonsillectomy resulted in an additional 22.9% [7.5, 35.2] reduction in AHI [95% confidence interval, CI] (P = .006), and 8.6 [1.7,43.4] (P = .010) greater odds [95% CI] of a successful treatment response with HGNS. Compared to historically poorer outcomes of HGNS in patients with OLW collapse, these early results suggest combining tonsillectomy with HGNS may represent a promising strategy to improve success rates.