Purpose <p>To evaluate arteriovenous fistula maturation and 12-month patency in patients undergoing oversized balloon angioplasty with high-pressure balloons alone or with high-pressure balloons plus drug-coated balloons as part of endovascular treatment for arteriovenous fistula maturation failure.</p> Material and Methods <p>This prospective, non-randomized study was conducted between 2022 and 2024 at four centers in Brazil. Patients with primary arteriovenous fistula failure underwent oversized balloon angioplasty with high-pressure balloons alone or with high-pressure balloons + drug-coated balloons. Vascular access primary and secondary patency rates were evaluated at 3, 6, and 12&#xa0;months in 198 patients. The safety endpoint was the incidence of procedure-related complications. Exploratory analyses included the impact of demographic and clinical variables on primary patency rates.</p> Results <p>Technical success was achieved in 99% of patients (196/198). At 12&#xa0;months, vascular access primary patency was 57.8% for high-pressure balloons + drug-coated balloons vs. 41.3% for high-pressure balloons alone (<i>p</i> = 0.011). Twelve-month vascular access secondary patency rates were similar between groups (88.5% for high-pressure balloons + drug-coated balloons vs. 87.0% for high-pressure balloons alone, p = 0.69). Cox regression analysis identified oversized balloon angioplasty with drug-coated balloons and male sex as protective factors, reducing the 12&#xa0;month risk of primary patency loss. In contrast, brachiocephalic arteriovenous fistulas and initial thrombosis were associated with an increased risk of patency loss.</p> Conclusion <p>Oversized balloon angioplasty with drug-coated balloons improved primary patency compared to high-pressure balloons alone.</p> Graphical Abstract <p></p>