Abstract Background Poorly controlled acute pain after surgery is associated with a variety of unwanted postoperative consequences, including patient suffering, distress, myocardial ischemia, prolonged hospital stay and increase of chronic pain. Neuraxial block is used for postoperative pain management and decrease analgesic use. Objective To compare the analgesic duration of intravenous and perineural administration of Dexamethasone in interscalene block during arthroscopic shoulder surgery. Patients and Methods Interventional randomized Double-Blind Study. This study was conducted in Ain Shams University Hospitals’ operating rooms throughout six months. In our study, 60 patients were randomly divided into two equal groups: Group A (30 patients) Block with 20 ml Bupivacaine 0.5% (+ 2 ml Dexamethasone ‘8 mg’) & 5 ml normal saline was injected IV. Group B (30 patients) Block with 20 ml Bupivacaine 0.5% (+ 2 ml normal saline) & 5 ml Dexamethasone ‘8 mg’ was injected IV. Results Our study showed that addition of 8 mg dexamethasone to bupivacaine in interscalene brachial plexus nerve block prolongs post-operative analgesia & reduced numbers of rescue analgesia doses more than injecting dexamethasone intravenously. Conclusion Addition of perineural dexamethasone to bupivacaine in interscalene brachial nerve block prolongs post-operative analgesia & reduced numbers of rescue analgesia doses more than injecting dexamethasone intravenously. Dexamethasone was seen to be a potent adjunct to local anaesthetic to prolong post-operative analgesia with negligible side effects.