Lower-extremity deep vein thrombosis (DVT) is prone to occur after internal fixation of tibial fractures. This study analyzed the effect of intramedullary nailing (IMN) and plate fixation (PF) on lower-extremity DVT, providing reliable reference and guidance for future clinical treatment of tibial fractures. Sixty-eight patients with tibial fractures admitted to Honghui Hospital, Xi'an Jiaotong University, between February 2019 and October 2020 were selected as research participants, of which 32 cases treated with open reduction and locking-compression plate fixation were assigned to the FP group and 36 cases treated with closed reduction and interlocking IMN were included in the FN group. The two groups were compared regarding the following items: clinical efficacy, operation, rehabilitation, joint function, pain, inflammatory factors (IFs), incidence of adverse reactions (ARs), blood loss, prognosis, and quality of life (QoL). The related factors affecting the occurrence of DVT were analyzed. The results identified no evident difference in the overall response rate between the two groups ( > 0.05). The FN group showed longer operation time, higher incidence of ARs, and better rehabilitation, while there were lower incision length, VAS score, and IF levels ( < 0.05). The results revealed no significant difference in estnimated blood volume(EBV) and the incidence of DVT between the two groups( > 0.05); however, the total blood loss (TBL), hidden blood loss (HBL), and blood transfusion rates in FN group were higher while the visible blood loss (VBL) was lower compared to the FP group ( < 0.05). Logistic regression analysis identified that blood transfusion, VBL, HBL, TBL, and treatment methods were independent risk factors affecting the occurrence of lower-extremity DVT ( < 0.05). In addition, the prognostic QoL was better in the FN group ( < 0.05). Therefore, closed reduction and interlocking IMN are more effective than open reduction and locking-compression plate fixation in the treatment of tibial fractures, but patients are more likely to suffer from lower-extremity DVT. In the future, it is necessary to carefully choose the treatment method in the treatment of tibial fracture patients to ensure their rehabilitation.