Objective To compare the safety and efficacy of the subxiphoid robot-assisted thoracoscopic surgery (SRATS) and intercostal robot-assisted thoracoscopic surgery (IRATS) for the treatment of anterior mediastinal tumors. Methods The clinical data of patients who received robot-assisted anterior mediastinal tumor resection in the same medical unit of the Department of Thoracic Surgery of Gansu Provincial Hospital from May 2020 to July 2022 were retrospectively collected. The patients were divided into a SRATS group and an IRATS group according to the surgical procedure. The perioperative data of patients were compared between the two groups. Results Finally 87 patients were collected, including 41 in the SRATS group (23 males and 18 females, mean age of 44.51±11.28 years) and 46 in the IRATS group (21 males and 25 females, mean age of 46.67±8.76 years). All 87 patients completed the surgery successfully. Compared with IRATS group, SRATS group had less intraoperative blood loss (24.41±6.67 mL vs. 37.93±9.23 mL, P=0.000), shorter postoperative catheterization time (1.73±0.59 d vs. 2.54±0.50 d, P=0.000), less postoperative drainage (94.46±34.08 mL vs. 116.72±24.90 mL, P=0.001), lower visual analogue score (VAS) on the first postoperative day (3.66±0.76 points vs. 4.15±0.84 points, P=0.005) and third postoperative day (2.41±0.59 points vs. 2.89±0.82 points, P=0.003), shorter postoperative hospital stay (4.12±0.81 d vs. 4.98±1.02 d, P=0.000) and lower hospitalization costs (45.1±6.5 thousand yuan vs. 48.6±6.8 thousand yuan, P=0.020). There was no significant difference in the operation time or the incidence of postoperative complications. Conclusion Both SRATS and IRATS have high safety and efficacy in the treatment of anterior mediastinal tumors. However, SRATS has less damage, which is more conducive to the rapid recovery of patients after surgery, and has a wide prospect of clinical application.