In order to investigate the perioperative changes in the levels of TAT (thrombin-antithrombin complex), PIC (plasmin-α₂-plasmin inhibitor complex), t-PAIC (tissue plasminogen activator-plasminogen activator inhibitor complex), and TM (thrombomodulin) in patients with lower extremity fractures, and to analyze their relationship with the occurrence of postoperative VTE (venous thromboembolism), a study was conducted on 100 patients who underwent surgery between January and July 2025. The patients were divided into a non-VTE group (76 cases) and a VTE group (24 cases) based on whether VTE occurred postoperatively. The levels of TAT, PIC, t-PAIC, TM, as well as FIB (fibrinogen) and D-D (D-dimer), were measured preoperatively and on postoperative days 1 and 3 in both groups. Correlations between these indicators and VTE were analyzed, multivariate logistic regression was used to explore risk factors for postoperative VTE, and ROC (receiver operating characteristic) curve analysis was performed to assess the predictive value of these thrombotic molecular markers for postoperative VTE. The results show that compared with the non-VTE group, the levels of FIB and D-D are elevated in the VTE group (P<0.05). Additionally, the levels of TAT, PIC, t-PAIC, and TM in the VTE group are significantly higher than those in the non-VTE group preoperatively and on postoperative days 1 and 3 (P<0.05). Correlation analysis reveales that TAT, PIC, t-PAIC, and TM were positively correlated with the occurrence of VTE (P<0.05). Multivariate logistic regression analysis indicates that FIB, D-D, TAT, PIC, t-PAIC, and TM are the main factors influencing the occurrence of VTE after lower extremity fracture surgery (P<0.05). ROC curve analysis demonstrates that the combined detection of TAT, PIC, t-PAIC, and TM had a high predictive value for postoperative VTE (P<0.05). It is concluded that elevated levels of thrombotic molecular markers in patients undergoing lower extremity fracture surgery are closely related to VTE formation, and the detection of these markers is clinically effective for predicting the occurrence of postoperative VTE.