Background Rarely, during the endoscopic thyroidectomy, carbon dioxide (CO2) embolism may occur. Methods Case 1: A 65-year-old female who was seen with prolonged fatigue and generalized bone pain was diagnosed primary hyperparathyroidism (PHPT) based on her preoperative biochemical profile. Transoral endoscopic parathyroidectomy vestibular approach (TOEPVA) was planned. Case 2: A 52-year-old male patient was seen with weakness and hepatosteatosis and was diagnosed PHPT based on the laboratory workup. TOEPVA was planned. Results After subplatysmal dissection with vascular tunnel probe, both of the patients developed severe bradycardia and hypotension leading to asystole during the CO2 insufflation. The possibility of CO2 embolism was considered and insufflation was terminated. After a successful cardiac massage, sinus rhythm returned. Conclusion TOEPVA may develop CO2 embolism leading to asystole during the CO2 insufflation.