Objective: To compare the clinical efficacies of integrated interventional therapy and systemic thrombolytic treatment for mixed type of acute lower extremity deep venous thrombosis (DVT). Methods: The clinical data of 458 patients with acute mixed type of lower extremity DVT admitted over 12 years were retrospectively analyzed. One-hundred and twenty-two patients (group A) underwent the integrated interventional therapy that comprised thrombus aspiration and thrombolysis, 53 cases who were complicated with iliac vein compression or obstruction received the auxiliary procedures of percutaneous transluminal angioplasty (PTA) and stent placement, and the other 107 patients (group B) received systemic thrombolytic therapy with urokinase and heparin. Results: The average length of hospital stay for patients in group A was (6.2±2.2) d and in group B was (6.2±2.2) d; the cure rate and effective rate reviewed 2 weeks later in group A was 40.98% and 14.02%, and in group B was 96.72% and 77.57%, respectively, and all differences between the two groups had statistical significance (all P<0.05). During 12–85 months follow-up period, the difference between the diameter of the two legs at 15 cm below knee joint was (0.53±0.42) cm in group A and (1.42±1.35) cm in group B; the incidence of edema, skin pigmentation, and ulceration was 23.15%, 9.26% and 0 in group A, and 50.51%, 80.81% and 9.09% in group B; the rates of vein patency and normal venous valve function were 81.48% and 57.41% in group A, and 65.66% and 15.15% in group B, respectively, and all the differences between the two groups had statistical significance (all P<0.05). Conclusion: Integrated interventional therapy has better short- and mid-term efficacy than systemic thrombolytic therapy for acute mixed type of lower extremity DVT, especially in the aspect of venous valves protection.