Background and Aims The incidence of thyroid carcinoma is continuously rising throughout the world. In clinical practice, the demand for endoscopic thyroidectomy has also increased. Among various approaches of endoscopic thyroidectomy, transoral endoscopic thyroidectomy vestibular approach (TOETVA) meets the concept of natural orifice transluminal endoscopic surgery (NOTES) better than other approaches. However, TOETVA is obviously associated with complications that may greatly affect patients' quality of life. Therefore, this study was conducted to evaluate the application efficacy of endoscopic thyroidectomy via oral vestibule and submandibular approach (ETOSA) in the treatment papillary thyroid carcinoma (PTC).Methods The clinical data of a total of 31 PTC patients undergoing ETOSA surgery in Xiangya Hospital from March 2022 to June 2022 were reviewed. The operative time, blood loss, postoperative drainage, length of postoperative hospitalization, pathological results, and the scores for neck cosmetic appearance, sensation of the submental area and postoperative pain as well as postoperative complications were analyzed.Results ETOSA procedure was successfully completed in all patients and none of them required a conversion to open surgery. The average operative time was (145.23±35.91) min, the mean intraoperative blood loss was (11.13±4.78) mL, the average drainage volumes were (50.97±26.25) mL on postoperative day (POD) 1 and (22.74±15.10) mL on POD 2 respectively, the average length of postoperative hospitalization was (2.19±0.47) d, and the average number of dissected central lymph node was 7.52±4.34. Complications such as postoperative hoarse voice, mental nerve injury, surgical area infection, swallowing discomfort, cracked corners of the mouth and swelling of the lower lip occurred in none of the patients. Only 2 cases had temporary hyperparathyroidism and 1 case had cervical skin perforation. All patients had no obvious lower lip and skin paresthesia with good cosmetic outcomes. Patients were satisfied with the recovery of the two 5-mm submental incisions.Conclusion ETOSA is a safe and feasible procedure, which can reduce the risks such as mental nerve injury and tears at the corners of the mouth and meanwhile avoid the possible interference between the instruments. So, it has certain clinical application value.