Objective To summarize the clinical data about mediastinal lesions, then to analyze the treatment effect of da Vinci robot system in the surgical treatment of mediastinal lesions. Methods We retrospectively analyzed the clinical data of 49 patients with mediastinal lesions in our hospital between January 2016 and October 2017. These patients were divided into two groups including a da Vinci robot group and a video-assisted thoracoscopic surgery (VATS) group according to the selection of the treatments. There were 25 patients with 14 males and 11 females at age of 56.5±17.9 years in the da Vinci group and 24 patient with 15 males and 11 females at age of 53.0±17.8 years in the VATS group. Results There was no statistical difference in surgery time between the two groups (t=–0.365, P=0.681). Less intraoperative blood loss (t=–2.569, P<0.001), less postoperative drainage amount within three days after surgery (t=–6.325, P=0.045), shorter period of bearing drainage tubes after surgery (t=–1.687, P=0.024), shorter hospital stays (t=–3.689, P=0.021), lower visual analogue scale (VAS) scores of postoperative 48 hours (t=–7.214, P=0.014) with a statistical difference in the da Vinci robot group compared with the VATS group. Conclusion The da Vinci robot system is safe and efficient in the treatment of mediastinal lesions compared with video-assisted thoracoscopic approach.