130 patients scheduled for major shoulder surgery were randomized to undergo the operative treatment with interscalene brachial plexus block and either perineural dexamethasone, intravenous dexamethasone, or saline solution. The purpose of this study was to determine if either administration of adjunct dexamethasone was associated with significantly improved block duration, opioid use, pain, and patient satisfaction up to 48 hours post-surgery. Results demonstrated that both administration methods of dexamethasone led to significantly increased duration of block, and reduced requirement of opioid and anti-emetic medications after follow-up period. Differences between perineural and intravenous dexamethasone administrations were comparable for all outcomes throughout the duration of the study.