Background: Thrombosis of native arteriovenous fistulas (AVFs) is a frequent cause of access failure in hemodialysis patients and requires prompt endovascular intervention to preserve access patency. This study compares AngioJet-assisted pharmacomechanical thrombectomy with thrombolysis and balloon maceration in terms of safety, efficacy, and long-term patency outcomes. Methods: This single-center retrospective cohort study included 292 consecutive patients treated for thrombosed native AVFs between 2021 and 2025. Patients underwent either AngioJet-assisted pharmacomechanical thrombectomy or thrombolysis with balloon maceration, with AngioJet selectively used in cases with higher thrombus burden and more complex lesion characteristics. Technical success, clinical success, periprocedural complications, primary, assisted primary, and secondary patency, as well as reintervention requirements were analyzed. Multivariable Cox regression was performed to identify independent predictors of patency and reintervention. Results: Both techniques demonstrated high technical and clinical success rates, comparable primary, assisted primary, and secondary patency outcomes, and low periprocedural complication rates with no major adverse events. Multivariable analysis identified thrombus burden, number of prior interventions, and anatomical factors—including cephalic arch stenosis as independent predictors of primary patency loss, whereas treatment modality was not. Reintervention was more frequent in patients with brachiocephalic fistula anatomy and active smoking. Conclusions: In thrombosed native AVFs, pharmacomechanical thrombectomy and thrombolysis with balloon maceration provide similar safety profiles and long-term patency outcomes. Patency and reintervention are primarily influenced by thrombus load, access anatomy, and patient-related factors rather than device selection, supporting a lesion-oriented and individualized endovascular treatment strategy.