Background: Interscalene brachial plexus block (ISB) is the gold standard for postoperative pain management in shoulder surgery. However, this technique has side effects and potentially serious complications. The aim of this study was to compare the combinations of ultrasound-guided suprascapular (SSB) associated with supraclavicular nerve block (SCB) and ultrasound-guided ISB for postoperative analgesia after shoulder instability surgery. Methods: Sixty ASA physical status I-II patients scheduled to undergo shoulder instability surgery were included. Two groups: (i) the SSB + SCB group (n = 30) in which the patients received a combination of US-guided SSB (15 mL of bupivacaine 0.25%) and US-guided SCB (15 mL of bupivacaine 0.25%) and (ii) the ISB group (n = 30) in which the patients received US-guided ISB with 30 mL of bupivacaine 0.25%. General anesthesia was administered to all patients. During the first 24h, the variables assessed were time to administer the anesthesia, duration of the analgesia, onset and duration of motor and sensory blockade, opioid consumption, cardiovascular stability, complications, and patient satisfaction. Results: Anesthesia induction took more time for the SSB + SCB group than for the ISB group. However, the onset time of motor and sensory blockade was similar in the two groups. Statistical analysis of the visual analog postoperative pain scoring at HO, H6, H12, and H24 showed nonsignificant differences between the groups. Analgesia, the first request for morphine, and total morphine consumption during the first 24 h was similar in both groups. No complication was recorded in the SSB + SCB group. However, phrenic nerve block occurred in all patients in the ISB group. Conclusion: US-guided SCB combined with US-guided SSB was as effective as ISB for postoperative analgesia after shoulder instability surgery without decreasing potential side effects. Trial registration: NCT identifier: NCT02397330. (C) 2016 Elsevier Masson SAS. All rights reserved.