ObjectiveThe 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.Study DesignCase‐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.SettingSingle academic institution.MethodsStudy outcomes were measures of HGNS efficacy defined as a %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 vs HGNS alone, independent variable) on HGNS efficacy. Analyses were adjusted for OLW collapse severity (complete vs partial), tonsil size, age, sex, body mass index, and baseline AHI.ResultsNineteen 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.ConclusionCompared 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.