Background: The management of failing hemodialysis arteriovenous fistulas (AVFs) is critical to ensuring continued dialysis access. This study evaluates and compares the effectiveness of drug-coated balloons (DCBs) versus plain old balloon angioplasty (POBA) in treating AVF stenosis, with a focus on primary patency rates, reintervention rates, and overall clinical outcomes. Methods: In this prospective randomized controlled trial, 48 patients with failing AVFs were enrolled and treated at Shebin Elkoom Teaching Hospital and Ain Shams University Hospital between 2023 and 2024. Participants were randomized into two equal groups: DCB group and POBA group. The primary outcome measures included primary patency rates at 6 months and 1 year, as well as the number of interventions required to maintain target lesion patency. Secondary outcomes included assisted primary patency, secondary patency rates, and safety outcomes, such as adverse events related to the arteriovenous access circuit.