Objective: To explore the possibility of reducing the use of antibiotics after transoral endoscopic thyroidectomy vestibular approach (TOETVA). Method: A retrospective study was conducted on patients with thyroid tumors who were diagnosed and underwent surgical treatment at our hospital from 2022 to 2024. Patients diagnosed with T1-stage differentiated thyroid cancer or a benign retrosternal goiter <4 cm with cosmetic needs were included in the current study. Drainage fluid was cultured on the first postoperative day. The differences in infection rates, bacterial culture results, and antibiotic use between patients with clean incisions and those with clean-contaminated incisions were compared. Results: There were no signs of infection in the postoperative drainage fluid or delayed healing due to surgical cavity infection. There was no significant difference in the incidence of postoperative infection or the results of bacterial culture between clean and clean-contaminated incisions or between the groups with and without antibiotic use for clean-contaminated incisions. The proportion of pathogenic bacteria in clean-contaminated incisions was significantly greater than that in clean incisions, while bacteria cultured in clean incisions were mostly common colonizing bacteria. Conclusion: Pathogenic bacteria may indeed exist in the operative cavity of the TOETVA regardless of whether antibiotics are used during the perioperative period. With adequate drainage, the absence of the routine administration of antibiotics or only preventive antibiotics during the perioperative period does not increase the infection rate.