PurposeTo evaluate the effect of drug-coated balloon (DCB) with high-dose paclitaxel for the treatment of restenotic dysfunctional arteriovenous fistulae (AVFs). Materials and MethodsIn this single-arm, multicenter, prospective, observational study, 334 patients using IN.PACT AV DCB (Medtronic, Plymouth, Minnesota) for the first time in the restenotic lesion of dysfunctional AVF between April 2021 and March 2022 were registered. ResultsProcedural success, defined as <30% residual stenosis, was achieved in 96.7% of cases. During a median follow-up of 7.4 months, 179 target lesion reinterventions (TLRs) were observed, and the 6-month freedom from TLR was 73.2% (68.2%–78.2%). When compared with the previous plain percutaneous transluminal angioplasty, the median time to reintervention was significantly longer with DCB (9.1 [8.0–10.6] vs 3.2 [3.0–3.4] months; P < .001). Baseline characteristics that were independently associated with TLR were as follows: months from the last intervention (adjusted hazard ratio, 0.50 [95% confidence interval, 0.40−0.62] per doubling; P < .001), partial lesion coverage by DCB (2.13 [1.10−4.12]; P = .024), and residual stenosis after DCB (2.19 [1.53−3.12] per 15% increase; P < .001) with its time interaction (0.91 [0.86−0.97] per month; P = .003). Of the 179 TLRs, 84 used DCB once again. The median time to reintervention was significantly longer for TLR using DCB (7.1 [6.2–9.7] vs 3.3 [3.1–4.0] months; P < .001). ConclusionsDCB with high-dose paclitaxel is effective at both the initial treatment in the restenotic lesion of dysfunctional AVF and during TLR after DCB use. However, partial lesion coverage by DCB and residual stenosis should be avoided.