Objective To investigate the effects of percutaneous vertebroplasty (PVP) on lumbar function, serum levels of prostaglandin E2 (PGE2) and substance P (SP) in patients with thoracolumbar compression fractures (TCF). Methods A total of 92 TCF patients who were treated in Xuchang Hospital of Traditional Chinese Medicine from January 2021 to May 2022, were collected and randomly divided into two groups, 46 cases in each group. The control group underwent percutaneous kyphoplasty (PKP), and the observation group underwent PVP. Perioperative indexes, serum levels of PGE2 and SP , imaging parameters (vertebral anterior margin height, vertebral Cobb angle), Oswestry disability index (ODI) before and after operation, and complications were compared between the two groups. Results The operation time, fluoroscopy times and hospitalization days in the observation group were less than those in the control group, the differences were statistically significant (P<0.05). After 7 days of operation, serum levels of SP and PGE2 in two groups were decreased compared with before operation, and the differences were statistically significant (P<0.05). After operation, the vertebral anterior margin height and vertebral Cobb angle in the observation group were better than those in the control group, and the differences were statistically significant (P<0.05). After operation, there was no significant difference in ODI between the two groups (P>0.05). There was no significant difference in the total incidence of complications between the two groups (10.87% vs 21.74%) (P>0.05). Conclusion PVP therapy in treatment of TCF patients can reduce serum levels of PGE2 and SP, improve lumbar function and promote postoperative recovery.