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Perineural dexamethasone and intravenous (IV) dexamethasone have been shown to prolong peripheral nerve block duration. The effects of perineural and IV dexamethasone have only been compared at doses of 4 mg or greater. This triple-blind, randomized trial examined the effect of 1 mg IV versus perineural dexamethasone on interscalene block (ISB) analgesia duration.Patients undergoing ambulatory shoulder arthroscopy received an ultrasound-guided ISB with 15 mL bupivacaine 0.5% and 1 mg preservative-free dexamethasone that was administered perineurally (PeriD) or IV (IVDex). All patients received IV ketorolac and were discharged on naproxen 500 mg 2 times a day plus oxycodone/acetaminophen as needed. Peripheral nerve block duration, pain, opioid consumption, and block satisfaction were assessed via telephone follow-ups.There were 63 PeriD patients and 62 IVDex patients who completed the primary outcome follow-up. The median time until analgesia from the ISB completely wore off was 3.5 hours (95% confidence interval, 1.0–6.0 hours) longer in the PeriD versus IVDex groups; P = 0.007). Time until the pain relief from the ISB began to wear off was also longer in the PeriD versus IVDex group (5.5 hours [95% confidence interval, 2.1–9.0 hours]; P = 0.002). Other secondary outcomes, including opioid consumption, satisfaction, and pain scores, were not different between groups.In patients undergoing shoulder arthroscopy, low-dose perineural dexamethasone (1 mg) in combination with 15 mL of 0.5% bupivacaine prolonged the median time until pain relief from the ISB completely wore off compared with 1 mg IV dexamethasone. However, the degree of prolongation was smaller than the a priori–defined minimal clinically meaningful difference of 5 hours.This study was registered at Clinicaltrials.gov, identifier NCT02506660.