Objective To compare the differences in the application of ultrasound scalpel and coagulation hook in thoracoscopic anterior mediastinal tumor surgery and to analyze the respective advantages and indications of the two commonly used energy instruments. Methods The clinical data of 85 patients undergoing thoracoscopic anterior mediastinal tumor surgery in West China Hospital of Sichuan University between June and November in 2017 were prospectively analyzed. There were 45 males and 40 females at age of 50.45 (18–75) years. The patients were divided into three groups including a ultrasound scalpel group (59 patients), a coagulation hook group (17 patients) and a mixed group (9 patients) according to the using time of energy devices. The clinical effect among the three groups were compared. Results No significant difference was found among the three groups in operation time, blood loss, average duration of chest tube drainage or volume of drainage (P>0.05). No significant complications occurred in all groups during operation or after operation. The proportion of subxiphoid approach in the ultrasound scalpel group was higher than that in the other two groups (49/59vs. 7/17 vs. 5/9, P<0.01). The maximum diameter of the tumor (4.58±2.19 cmvs. 4.05±1.07 cm vs. 3.00±1.45 cm, P<0.05) and the resected tissue weight (103.67±74.78 gvs. 61.17±31.97 g vs. 61.86±34.13 g, P<0.05) were also significantly greater than that in the coagulation hook group or the mixed group. Conclusion Ultrasound scalpel has good safety and reliability in the thoracoscopic anterior mediastinal tumor surgery, and is more suitable for operation in a narrow space.