Objective <p>To evaluate the safety and efficacy of drug-coated balloon (DCB) and conventional balloon (CB) in the treatment of venous stenosis in hemodialysis access.</p> Method <p>The clinical data of 403 hemodialysis patients with arteriovenous fistula stenosis who were admitted to our hospital from November 1, 2020 to January 1, 2024 were retrospectively analyzed and divided into DCB group (<i>n</i> = 163) and CB group (<i>n</i> = 240). The Kaplan-Meier curve was used to evaluate the target lesion primary patency (TLPP) of the two groups. The primary endpoint was the primary patency rate of target lesions 12 months after surgery, and the secondary endpoints were the primary patency rates of target lesions 6 months, 18 months, and 24 months. Cox proportional hazard models were applied to explore the association between DCB and the risk of hemodialysis access dysfunction.</p> Results <p>The primary patency rate of target lesions in DCB group was higher at 6 months, 12 months, 18 months and 24 months, and the difference was statistically significant at 6 months (85.0% VS 69.3%, <i>P</i> = 0.0109) and 12 months (64.6% VS 38.0%, 0.0300).There was no significant difference at 18 months (36.9% VS 14.9%, <i>P</i> = 0.1475) and 24 months (23.1% VS 7.5%, <i>P</i> = 0.5091). The median survival time of DCB group was 449 days, and that of CB group was 270 days. The patency time of DCB group was significantly higher than that of CB group (<i>P</i> &lt; 0.0001). After full covariate adjustment, the analysis revealed that patients in DCB group (HR: 0.34, 95% CI: 0.16, 0.70) had a significantly lower risk of hemodialysis access dysfunction compared to those in CB group.</p> Conclusion <p>The results show that compared with CB, DCB can obviously improve the primary patency rate of target lesions with vascular access stenosis in hemodialysis and reduce the re-intervention of target lesions, which is an effective and safe treatment for hemodialysis patients.</p>