Objective <p>This study aimed to observe the patency outcomes in patients with arteriovenous fistula (AVF) stenosis treated with paclitaxel-coated high-pressure balloon angioplasty.</p> Methods <p>Eighty patients with AVF stenosis were randomly assigned to two groups (<i>n</i> = 40 each). The control group underwent conventional balloon angioplasty, while the observation group received paclitaxel-coated high-pressure balloon angioplasty. Baseline characteristics were recorded. Changes in vascular diameter, dialysis blood flow, and peak systolic velocity at the stenotic site were compared pre- and post-treatment. Surgical success rate and restenosis rates were recorded. Fistula patency was followed at multiple postoperative time points, and postoperative quality of life was assessed using the WHOQOL-BREF scale.</p> Results <p>Baseline characteristics were comparable between the two groups (<i>P</i> &gt; 0.05). Following the treatment, the observation group demonstrated greater improvements in vascular diameter, dialysis blood flow, and peak systolic velocity than the control group (<i>P</i> &lt; 0.05). Although technical success did not differ markedly, the observation group experienced a lower rate of restenosis (<i>P</i> &lt; 0.05). Fistula patency rates at 3–9 months postoperatively showed no significant difference (<i>P</i> &gt; 0.05), but at 12 months, the observation group exhibited higher patency rates (<i>P</i> &lt; 0.05). Postoperative quality-of-life scores were higher in the observation group (<i>P</i> &lt; 0.05).</p> Conclusion <p>Paclitaxel-coated high-pressure balloon angioplasty may offer notable benefits for AVF stenosis, including enhanced long-term patency, and reduced restenosis, ultimately contributing to better patient-reported quality of life.</p>