Objective: To investigate the efficacy of DSA-guided posterior/anterior tibial vein puncture and catheter-directed clot fragmentation/thrombolysis for acute lower extremity deep venous thrombosis (DVT). Methods: From August 2012 to November 2016, 87 patients with mixed type and central type acute lower extremity DVT underwent DSA-guided posterior/anterior tibial vein puncture and catheter-directed clot fragmentation/thrombolysis. Effectiveness evaluation was performed by comparison of the limb circumference differences before and after thrombolysis and observation of the angiographic evidence of deep venous patency after thrombolysis. Results: Of the 87 patients, successful puncture was performed in 80 cases (91.9%), of whom 68 cases underwent posterior tibial vein puncture and 12 cases underwent anterior tibial vein puncture; 7 cases with failed puncture underwent catheterization by posterior tibial vein incision. Clot fragmentation combined with catheter-directed thrombolysis was performed in all patients after successful catheterization. Compared with findings before thrombolysis, the limb circumference difference was significantly reduced [(4.28±1.02) cm vs. (1.06±0.42) cm] and venous patency score was significantly decreased [(10.25±1.84) vs. (1.92±0.5)], and all differences had statistical significance (all P<0.05). Conclusion: DSA-guided posterior/anterior tibial vein puncture and catheter-directed clot fragmentation/thrombolysis is a simple and effective method for treatment of acute lower extremity DVT.