Purpose: To compare all-cause mortality and primary patency with drug-coated balloon angioplasty (DCBA) compared with plain balloon angioplasty (PBA) in people with hemodialysis-related stenosis. Materials and methods: PubMed, Embase, and Cochrane Library databases were searched from November 1966 to February 2021 to identify randomized controlled trials (RCTs) that assessed the use of DCBA versus PBA for stenosis in hemodialysis circuits. Data extracted from the articles were integrated to determine all-cause mortality, target lesion primary patency (TLPP), circuit access primary patency (CAPP), 30-day adverse events, and technical success for the two approaches. We performed meta-analysis on these results using a fixed-effects model to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) where I-2 < 50% in a test for heterogeneity, or a random-effect model if otherwise. Sensitivity and subgroup analyses were also performed. Results: Sixteen RCTs of 1672 individuals were included in our meta-analysis, of which 839 individuals received DCBA and 833 received PBA. The pooled outcome showed no statistical difference between DCBA and PBA in all-cause mortality at 6 months (OR = 1.29, 95% CI = 0.72-2.32, p = 0.39, I-2 = 4%), 12 months (OR = 1.02, 95% CI = 0.68-1.53, p = 0.91, I-2 = 0%), and 24 months (OR = 1.50, 95% CI = 0.87-2.57, p = 0.15, I-2 = 0%), 30-day adverse events (OR = 1.09, 95% CI = 0.30-3.98, p = 0.90, I-2 = 66%), and technical success (OR = 0.18, 95% CI = 0.02-1.92, p = 0.16, I-2 = 65%). The DCBA had significantly better outcomes versus PBA in TLPP at 6 months (OR = 2.37, 95% CI = 1.84-3.04, p < 0.001, I-2 = 44%) and 12 months (OR = 1.77, 95% CI = 1.22-2.56, p = 0.002, I-2 = 56%), and CAPP at 6 months (OR = 2.07, 95% CI = 1.21-3.54, p = 0.008, I-2 = 67%) and 12 months (OR = 1.66, 95% CI = 1.29-2.15, p < 0.001, I-2 = 0%). Conclusion: In hemodialysis circuit stenosis, DCBA appears to have similar safety but greater efficacy than PBA.