280 patients scheduled for arthroscopic shoulder surgery under an interscalene brachial plexus block (ISB) with 30 ML bupivacaine were randomized to adjuvant 4mg perineural dexamethasone, 8mg perineural dexamethasone, 4mg intravenous dexamethasone, or 8mg intravenous dexamethasone in this factorial designed study. The primary goal of this study was to evaluate if route or dose of adjuvant dexamethasone had a significant effect on analgesic duration. Results demonstrated that the difference in effect between the route of dexamethasone significantly favour perineural dexamethasone to intravenous dexamethasone, though it was unclear if the difference was clinically relevant at approximately 2 hours (95%CI 0.4-3.5hrs). The difference in effect between 4mg and 8mg doses was not significant (MD 1.3hr [95%CI -0.3, 2.9]; p=0.1). The mean (95%CI) analgesia durations of the blocks were 24.0hr (22.9 to 25.1), 24.8hr (23.2 to 26.3), 25.4hr (23.8 to 27.0), and 27.2hr (25.2 to 29.3) for intravenous doses of 4 and 8 mg and perineural doses of 4 and 8 mg, respectively.