IMPORTANCE: Allergic contact reactions to medical implants are underrecognized and incompletely understood, particularly in hypoglossal nerve stimulation (HGNS), an increasingly popular and effective alternative to positive airway pressure therapy for patients with obstructive sleep apnea (OSA). OBJECTIVE: To document a rare case of allergic contact reaction in a patient following implantation of an HGNS device for OSA. DESIGN, SETTING, AND PARTICIPANT: In this case report, the patient presented to a quaternary care academic medical center with localized erythema, swelling, and pustular drainage at the right neck incision site approximately 2 months following HGNS device implantation. EXPOSURE: This patient underwent serial, bilateral HGNS device implantation and subsequent explantation. MAIN OUTCOME AND MEASURE: The main outcomes were the findings from symptom monitoring and allergy patch testing. RESULTS: A 64-year-old male patient with severe OSA (Apnea-Hypopnea Index, 54 events/h) underwent implantation of an HGNS device. His recovery was uneventful for 2 months until he reported localized erythema, swelling, and pustular drainage at the right neck incision site. HGNS device extrusion at the neck was noted approximately 3 months postoperatively, prompting device explantation. The patient underwent subsequent HGNS reimplantation in the left neck and chest 3 months after right-sided explantation. At postoperative day 10, swelling, erythema, and purulence were noted from neck and chest incisions. The device was re-explanted with odorless purulence noted in the chest and neck. The wound cultures were negative for infection, and at this time, the patient underwent allergy patch testing, which demonstrated a strong positive reaction to isophorone diisocyanate. Patch testing confirmed an allergy to isocyanates, evidenced by a strong positive reaction to isophorone diisocyanate, 1.0%, in petrolatum. This finding was further validated by the manufacturer, which confirmed isocyanates were used in the polyurethane components of the HGNS device. CONCLUSIONS AND RELEVANCE: Isocyanates are low-molecular weight compounds used in the production of polyurethanes, which are commonly found in medical devices. HGNS is a widely available implantable medical device for treatment of patients with OSA. The literature regarding isocyanate allergies with medical implants is limited, and this may be the first confirmed case with an HGNS device. This case report highlights the importance of noninfectious causes of device reactions, especially when occurring outside of the postoperative wound infection window. Patch testing for isocyanate and other components can inform both patient and clinician regarding the cause of device implantation failure and have implications for future implantable devices.