Objective The purpose of this study is to evaluate the efficacy and safety of endovascular management of central venous obstruction (CVO) in chronic renal failure (CRF) patients depending on arteriovenous access. Patients and methods A prospective study was done at the Vascular Surgery Department, Zagazig University Hospitals, Egypt and Intervention Radiology Department, Alnoor Specialist Hospital, Makkah, Saudi Arabia, from July 2015 to December 2018. Twenty-five endovascular interventions were performed in 21 CRF patients with vascular accesses and symptomatic CVO. Seventeen (81%) patients reported insertion of central venous catheters. The study included 12 men and nine women. The mean age was 51±9.5 years (range: 36–65 years). The mean duration of arteriovenous access was 10±3.5 months (range: 2–17 months). The lesions were occlusion in 12 (57.1%) patients and significant stenosis in nine (42.9%) patients. The mean lesions length was 4.5±1.5 cm (range: 2–7 cm). Results Technical success occurred in 17 (81%) patients. Percutaneous transluminal angioplasty was done in 12 patients and stenting was done in five patients. We failed in four patients. Early complications occurred in three (14.3%) patients in the form of dissection in one patient, and limited contrast extravasation in two patients. Late complications occurred in five (23.8%) patients within 4–10 months in the form of restenosis in four patients and thrombosis of access in one patient. Mean intervention-free period was 5.1 months. The primary patency rates were 70.1% at 6 months and 53.5% at 12 months and secondary patency rates were 75.3 and 63.9% at 6 and 12 months, respectively Conclusion Endovascular management of CVO can be used safely in CRF patients with good results at the short run, but for long run results, regular follow-up and reinterventions are mandatory. Decreasing insertion of central venous catheters, especially in the subclavian vein, is the main prophylaxis against CVO