Abstract： Objective To explore the effect of subxiphoid three-port video-assisted thoracoscopic surgery on periopera-tive indicators and stress complications in patients with anterior mediastinal tumors.Methods 68 patients who underwent video-assisted thoracoscopic resection of anterior mediastinal tumors were selected,and divided into 2 groups according to the different surgical approaches,each with 34 cases.Group A was performed via lateral thoracic approach,while group B was via subxiphoid three-port approach.Then the evaluation criteria including perioperative indicators,stress response,and postoperative complica-tions were compared between groups.Results In terms of perioperative indicators,the operation duration,intraoperative blood loss,days with drainage and postoperative length of stay yielded no statistical difference between the 2 groups(P＞0.05),while group B had decreased time to first out-of-bed activity and shorter time of postoperative analgesic use than those of group A(P＜0.05).Group B scored lower on VAS than group A at postoperative d2 and d3(P＜0.05).The pain substances and stress re-sponse substances cortisol(Cor),prostaglandin E2(PGE2)and substance P(SP)were all above normal values,and the 3 indica-tors were all higher in group B than in group A(P＜0.05).No statistical difference was found in the incidence rate of lung infec-tions,pulmonary leakage,arrhythmia,atelectasis,pleural effusion,and abnormal skin sensation between the 2 groups(P＞0.05),while the overall complication rate of group B was lower than that of group A(P＜0.05).Conclusion The treatment of anterior mediastinal tumors through subxiphoid three-port video-assisted thoracoscopic surgery can significantly alleviate perioperative pain,attenuate postoperative stress response,and effectively reduce the incidence of complications such as atelectasis,pleural effu-sion,and skin sensory abnormalities.