Background and Aims Acute inferior vena cava thrombosis (IVCT) commonly occurs secondary to inferior vena cava filter (VCF) implantation. If not promptly treated, it may lead to serious complications such as bilateral lower limb swelling and pulmonary embolism and can also reduce the likelihood of successful filter retrieval. Percutaneous mechanical thrombectomy (PMT) and catheter-directed thrombolysis (CDT) are currently the main interventional treatments for IVCT, but comparative studies evaluating their efficacy and safety remain limited. This study was to conduct a prospective randomized controlled trial to compare the clinical efficacy and safety of AngioJet mechanical thrombectomy versus conventional CDT in the treatment of acute IVCT and to explore factors influencing filter retrieval rates, thereby providing evidence-based guidance for clinical decision-making.Methods From January 2022 to December 2024, patients diagnosed with acute IVCT following VCF implantation were prospectively enrolled at the Department of Vascular Surgery, Beijing Jishuitan Hospital, Capital Medical University. Patients were randomly assigned to either the CDT group (n=46) or the PMT group (n=48) according to the interventional procedure used. The two groups were compared in terms of filter retrieval rates, thrombus clearance outcomes, operative time, thrombolytic drug dosage, and incidence of complications. Logistic regression analysis was used to identify factors associated with primary filter retrieval.Results A total of 94 patients were enrolled, with 46 in the CDT group and 48 in the PMT group. Compared to the CDT group, the PMT group demonstrated a significantly higher primary filter retrieval rate (77.1% vs. 43.5%), grade Ⅲ thrombus clearance rate (70.8% vs. 37.0%), and better postoperative thrombus scores. Additionally, the PMT group required lower urokinase doses and shorter thrombolysis duration (all P<0.05). The overall filter retrieval rate and 3-month IVC patency were similar between groups, both exceeding 93%. Regarding safety, the CDT group had a higher incidence of catheter-related infections and medical adhesive-related skin injury, while vagal reflex symptoms were more frequent in the PMT group. Logistic regression analysis identified thrombus clearance rate as an independent factor significantly associated with primary filter retrieval in the PMT group (OR=190.773, P<0.05).Conclusion Compared to CDT, AngioJet mechanical thrombectomy combined with manual aspiration achieves higher thrombus clearance and primary filter retrieval rates in the treatment of acute IVCT while also reducing thrombolysis duration and drug dosage. However, attention should be paid to the increased risk of vagal reflex symptoms. There was no significant difference between the two groups in secondary filter retrieval rates or long-term IVC patency. The choice of intervention should be based on the patient's condition, timing of filter retrieval, and individualized clinical considerations.