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Objectives The objective of this study was to evaluate the efficacy and safety in patients with acute lower extremity deep venous thrombosis who underwent pharmacomechanical thrombectomy (PMT, AngioJet mechanical thrombus aspiration). Methods In this retrospective, 424 consecutive patients with acute lower extremity deep venous thrombosis from three institutions were enrolled in the study from January 2015 to December 2018. Of these, patients were divided into two groups, AngioJet group ( n = 186) and catheter-directed thrombolysis (CDT) group ( n = 238). Evaluation indexes including limb circumference difference, length of stay (LOS), urokinase dosage, periprocedural complications, follow-up imaging findings and villalta scores were analyzed from the medical records. Results A total of 424 patients diagnosed with acute lower extremity deep venous thrombosis were collected in this study. These patients were categorized into AngioJet group and CDT group. Significant differences were observed between the two groups with respect to the thigh circumference difference (5.32 ± 1.85 cm vs. 4.69 ± 2.15 cm; p = 0.04), calf circumference difference (2.79 ± 1.54 cm vs. 2.35 ± 1.25 cm; p = 0.01), thigh detumescence rate (72.19 ± 19.55% vs. 65.35 ± 17.26%; p = 0.00) and calf detumescence rate (62.79 ± 18.56% vs. 55.75 ± 17.27%; p = 0.00). The mean dose of urokinase in AngioJet group was 95.16 ± 45.89 million IU significantly less than that in the CDT group 293.76 ± 42.71 million IU ( p = 0.00). The overall bleeding complication rate was 9.91% (19 patients in AngioJet group and 23 patients in CDT group), which included three major (0.71%, 3/424) and 39 minor (9.2%,39/424) events. In the AngioJet group, serum creatinine (sCr) concentration and urine erythrocyte from the hemolysis caused by the mechanical process were higher than baseline data at admission ( p = 0.00, p = 0.00). The postoperative red blood cell and hemoglobin in two groups were lower than baseline data ( p = 0.00, p = 0.00). Compared with CDT, AngioJet thrombectomy has significantly lower estimated incidence of PTS in the follow-up. Conclusion AngioJet thrombectomy has stronger clearance ability for acute lower extremity deep venous thrombosis leading to significant reduction in the consumption of hospital resources, total dose of thrombolytic agents, and infusion time, thereby preventing adverse bleeding events, but patients with renal insufficiency should be careful. Ideal short-term and medium-term efficacy and safety are certain.