Purpose: To compare primary patency rates and target lesion revascularization of paclitaxel-coated balloon (PCB) versus plain balloon angioplasty (PBA) to preserve the patency of the vascular access circuit in patients undergoing hemodialysis after one year of follow-up.   Patients and methods: Within 24-month period, during 2015 and 2016, 96 patients (54 men=56%; mean age 60.3±13.8) with hemodialysis-dependent end-stage renal disease were enrolled in the study. In total, 48 patients were randomly assigned to group PCB (29 AVGs & 19 AVFs) & 48 patients to group PBA (29 AVGs & 19 AVFs). Baseline & procedural variables were comparably distributed in PCB & PBA groups.   Results: There were no significant differences in age of the treated vascular access circuit (2.31±1.62 years in PCB group vs. 2.63±1.94 years in PBA group, p=0.483), nor in the overall length of the treated target vein lesion (5.2±1.4 cm in PCB group vs. 5.4±1.6 cm in PBA group, p=0.641). All patients enrolled in the study completed the 1-year follow-up period. Device success rates were 100% in the PBA group and 39.6% in the PCB group, as further dilation with PBA was needed in 29 of 48 cases (60.4%) in the PCB group to achieve acceptable immediate postprocedural residual stenosis less than 30% (p=< 0.001). Anatomic and clinical success rates were 100% in both groups. No minor or major procedure- related complications occurred in either group. TLR free survival was significantly superior in the PCB group according to the Kaplan–Meier survival analysis curve (PCB, 316 days; PBA, 172 days; p=0.041), access circuit primary patency results were also significantly in favor of PCB angioplasty (PCB, 287 days; PBA, 156 days; p = 0.04). There were three cases in the PBA group (15%) and four cases in the PCB group (20%) in which lesions had been treated in a previous session with a PBA. There was no statistically significant difference in this subgroup analysis (p>0.1).   Conclusion: In this three-center study, paclitaxel-coated balloon angioplasty results in improved vessel patency and is superior to plain balloon dilation in the treatment of venous stenoses of failing native or prosthetic arteriovenous shunts used for dialysis access. In the PCBs group, additional HPB postdilatation was required in the majority of cases. These results combined with the “do not leave any metal behind" principle, characteristic in balloon angioplasty, marks paclitaxelballoon as a really promising technology and merits larger-scale trails for PCBs to have a future place in the armamentarium for the treatment of venous stenosis in failing dialysis access.