Objective To study the effect of negative pressure wound therapy (NPWT) on the prevention and treatment of orifice complications after endoscopic thyroidectomy (ETE) through chest-breast approach.Methods From June 2020 to September 2021, 48 patients underwent ETE were randomly divided into treatment group (NPWT group) and control group (traditional compression group) with 24 cases in each group. The operation time, intraoperative blood loss, postoperative drainage volume, length of postoperative hospitalization, and the incidence of operation and orifice complications between the two groups were compared.Results There were no statistically significant differences in the operation time, intraoperative blood loss and the incidence of operation complications between the two groups (P > 0.05). The postoperative drainage volume of the treatment group was less than that of the control group, the postoperative hospital stay was shorter than that of the control group, and the incidence of subcutaneous cavity effusion was lower than that of the control group, and the differences between the two groups were statistically significant (P < 0.05).Conclusion NPWT can obviously reduce the incidence of subcutaneous cavity effusion of ETE with chest-breast approach, moreover, it was beneficial to patients’ rapid recovery after surgery.