Background Digital subtraction angiography and thrill palpation demonstrate limitations when used to assess the outcomes of angioplasty in autologous arteriovenous fistulas (AVFs). Purpose To investigate a new functional quantifiable index of successful angioplasty for failing AVFs using intraprocedural percutaneous US volume flow (VF) measurements. Materials and Methods This prospective, multicenter, single-arm, cohort clinical trial included consecutive patients with indications for fluoroscopically guided balloon angioplasty due to AVF dysfunction between June 2020 and May 2022. Intraprocedural VF measurements were obtained before the procedure and after balloon dilation using transcutaneous duplex US. The primary end points were the quantification of VF-guided angioplasty outcomes and assessment of the association between postprocedural VF and freedom from target lesion reintervention (TLR) due to recurrence of access failure. Cox multivariate regression analysis was performed to identify predictors of TLR-free survival, which was estimated using Kaplan-Meier methods. Receiver operating characteristic curve analysis was used to determine the optimal cutoff VF value. Results In total, 100 participants (mean age, 67 years ± 12 [SD]; 84 male) were evaluated. The rate of freedom from TLR was 73% at 6 months. The mean pre- and postintervention VF values were 353 mL/min ± 199 and 1045 mL/min ± 413, respectively. Higher VF at completion of angioplasty (hazard ratio, 0.89 per 100 mL/min [95% CI: 0.82, 0.98]; P = .01) and forearm versus upper arm AVF (hazard ratio, 0.51 [95% CI: 0.27, 0.95]; P = .03) were independent predictors of increased freedom from TLR. A postprocedural VF of 720 mL/min (P < .001) was identified as the optimal cutoff point for predicting increased fistula freedom from reintervention and freedom of restenosis for radiocephalic AVFs, compared with an optimal cutoff point of 1120 mL/min (P = .03) for upper arm AVFs. Conclusion Intraprocedural VF measurement is a quantifiable functional index and postprocedural predictor of outcomes following angioplasty for failing dialysis AVFs. ClinicalTrials.gov identifier: NCT04694287 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Prince et al this issue.