Purpose Although intravenous sedation and analgesia have been widely used as a first choice to relieve pain during treatment of dysfunctional hemodialysis fistulas by interventional radiology, the sedoanalgesic drugs have a considerable risk of respiratory depression, especially in hemodialysis patients. In this study, we compared the utility and efficiency of ultrasound-guided supraclavicular brachial plexus block versus sedoanalgesia for the prevention of pain during endovascular treatment of dysfunctional hemodialysis fistulas Materials and Methods Patients were randomized into two groups: ultrasound-guided supraclavicular brachial plexus block (n = 34) or sedoanalgesia group (n = 34). A visual analogue scale from no pain (= 0) to worst pain possible (= 10) was used to assess the pain intensity. Patient and operator satisfaction were graded from 0 to 2: 0, not satisfied at all; 1, partially satisfied; 2, satisfied (very well or complete satisfaction). Both groups were compared in terms of pain scores, patient and operator satisfaction as well as complications. Results The median pain score was significantly lower in the block group compared to the sedoanalgesia group, 0 (0-4) versus 6 (2-10), p = 0.0001. Patient satisfaction and operator satisfaction were significantly higher in the block group than in the sedoanalgesia group (p = 0.0001). Severe oxygen desaturation occurred in five (14.7%) patients following the administration of sedoanalgesia. No side effects or complications related to block procedure occurred in any patient. Conclusion Ultrasound-guided supraclavicular brachial plexus block has advantages over the sedoanalgesia during endovascular treatment of dysfunctional hemodialysis fistulas. It can provide safe and efficient analgesia with excellent procedural satisfaction in adult hemodialysis patients.