Objective: To investigate the influence of Huoxue Sanyu Xiaozhong Zhitong decoction combined with lateral approach-assisted modified posteromedial approach surgery on affected limb swelling, joint function and stress in patients with posterior Pilon fractures. Methods: A total of 104 patients with posterior Pilon fractures admitted to the hospital from January 2023 to December 2024 were included and randomly divided into combined group (n=52) and control group (n=52). The control group was treated with lateral approach-assisted modified posteromedial approach surgery and postoperative routine treatments such as anti-infection, analgesia and staged rehabilitation guidance, while the combined group was given Huoxue Sanyu Xiaozhong Zhitong decoction on the basis of the control group. The changes of affected TCM syndrome score, limb swelling degree (swelling degree grading, bilateral ankle circumference difference), joint function and lower limb motor function [ankle activity (AOFAS ), Fugl-Meyer assessment (FMA)], pain visual analogue scale (VAS) and serum stress indexes [angiotensin II (ATII), cortisol (Cor), norepinephrine (NE)] were compared between the two groups of patients before and after treatment. Results: The TCM syndrome score, swelling degree grading, ankle circumference difference and VAS score in the two groups at 4 weeks after surgery were significantly reduced compared with those before surgery, and the levels of ATII, Cor and NE in the two groups at 7 days after surgery were also significantly reduced than those at 1 day after surgery, and the above indexes in combined group were also significantly lower than those in control group (P<0.05). The AOFAS score and FMA score were significantly enhanced compared with those before surgery, and the scores in combined group were higher than those in control group (P<0.05). Conclusion: Huoxue Sanyu Xiaozhong Zhitong decoction combined with lateral approach-assisted modified posteromedial approach surgery can significantly alleviate postoperative swelling, relieve pain and promote joint function recovery in patients with posterior Pilon fractures. Its mechanism may be related to the inhibition of stress response, and it is worthy of clinical promotion in department of orthopedics.