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Intravenous (IV) dexmedetomidine (DEX) is reported to prolong the analgesic duration after single-shot interscalene brachial plexus block (ISBPB). However, the effective analgesic dose of IV DEX remains undetermined. Therefore, we aimed to elucidate the clinically relevant dose of IV DEX to prolong the analgesic duration of ISBPB.Seventy-two patients scheduled for arthroscopic shoulder surgery received ISBPB with 15 mL of 0.5% ropivacaine with 1:200,000 epinephrine and were randomly assigned to 1 of 4 groups (n = 18, each): (1) IV normal saline (control), (2) IV DEX 0.5 μg/kg (DEX 0.5), (3) IV DEX 1.0 μg/kg (DEX 1.0), and (4) IV DEX 2.0 μg/kg (DEX 2.0). The primary outcome was time to the first pain at surgical site.The median (interquartile range) duration of analgesia was significantly prolonged for the DEX 2.0 (874 minutes [727–1153 minutes]) compared with 656 minutes (590–751 minutes), 703 minutes (644–761 minutes), and 696 minutes (615–814 minutes) for the control, DEX 0.5 and DEX 1.0 groups, respectively (P = 0.001, P = 0.008, and P = 0.003, respectively). Postoperative cumulative IV morphine equivalent consumption at 24 hours was significantly lower in the DEX 2.0 compared with the control, DEX 0.5 and DEX 1.0 groups (P < 0.001, P < 0.001, and P = 0.007, respectively). There were no significant differences in the incidence of intraoperative hypotension and the number of patients who required ephedrine after the pairwise group analysis. Also, there were no significant differences on the durations of motor blockade and sedation and the incidence of bradycardia.Intravenous DEX at a dose of 2.0 μg/kg significantly increased the duration of ISBPB analgesia without prolonging motor blockade and reduced the cumulative opioid consumption at the first 24 hours in patients undergoing arthroscopic shoulder surgery.This study was registered at the Clinical Trial Registry of Korea, identifier KCT0002119.