BACKGROUND: Stenosis in arteriovenous fistulas (AVF) due to neointimal hyperplasia is one of the most common causes of hemodialysis vascular access dysfunction. Treating patients with dysfunctional AVF with drug-coated balloon (DCB) angioplasty may potentially improve outcomes. OBJECTIVES: This systematic review aimed to compare the effectiveness and safety of DCB angioplasty versus conventional balloon angioplasty by pooling evidence from the most recent randomized controlled trials. METHODS: We conducted a comprehensive literature search in the Web of Science, Embase, and Cochrane central databases. Two independent researchers screened the article, extracted interest, and evaluated included studies for risk of bias. Pooled estimation was conducted in terms of 6-month target-lesion primary patency (TLPP) and target-lesion reintervention (TLR), as well as other outcomes. RESULTS: Results were expressed with odds ratio (OR) and 95% confidence interval (CI). A total of five RCTs were identified and included in the meta-analyses, with 1107 participants. DCB has a trend of a higher rate of TLPP (OR 1.79, 95% CI 0.66-4.90, CONCLUSION: DCB may be an alternative treatment of dysfunctional AVF given a trend of a higher rate of TLPP and a significantly lower rate of TLR than conventional balloon angioplasty within 6 months after the indexed procedure. Moreover, DCB was non-inferior to conventional balloon angioplasty in terms of safety. Considering variations in the DCB technique, further studies are warranted for a standardized process.