Objective To investigate the clinical efficacy and safety of aspiration thrombectomy combined with anticoagulant therapy in patients with acute deep vein thrombosis (DVT) of the lower extremities, and to evaluate its effects on coagulation function, resolution of lower extremity swelling, short-term efficacy, and incidence of complications. Methods A retrospective analysis was conducted on 100 patients with acute-phase lower limb DVT admitted to Tianjin Union Medical Center from January 2022 to December 2024. Patients were divided into an observation group (n=50, aspiration thrombectomy combined with anticoagulant therapy) and a control group (n=50, anticoagulant therapy alone) based on treatment protocols. Both groups received a low-molecular-weight heparin bridging regimen followed by oral rivaroxaban, supplemented with batrobin and sodium saponin. The observation group additionally underwent 10F catheter-based negative pressure thrombectomy. Coagulation function parameters , leg circumference difference, treatment efficacy grading, and incidence of major complications were compared between the two groups before surgery and on the third day post-surgery, including prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and D-dimer (D-D). Results On the third day postoperatively, there was no statistically significant difference between the observation group and the control group in terms of PT (P>0.05); however, the observation group showed superior outcomes compared to the control group in terms of prolonged APTT, decreased FIB, and reduced D-dimer levels (all P<0.05). On the third day postoperatively, the difference in circumference between the thigh and calf was significantly smaller in the observation group than that in the control group (P<0.05). Compared with the control group, the observation group showed significantly higher excellent response rate and overall response rate (52.17% vs. 20.37%, 93.48% vs. 74.07%, all P<0.05). There was no statistically significant difference in the incidence of complications such as pulmonary embolism and mild bleeding between the two groups (P>0.05), but the filter retrieval rate was significantly higher in the observation group than that in the control group (P<0.05). Conclusion Aspiration thrombectomy combined with anticoagulant therapy can effectively improve coagulation status, reduce limb swelling, and enhance short-term efficacy in patients with acute DVT, without significantly increasing the risk of complications such as bleeding, demonstrating high clinical application value.