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Research suggests that the addition of dexmedetomidine to local anesthetics can prolong peripheral nerve blocks; however, clinical safety data are limited, and interscalene blocks have not been studied. The present study was designed to test the hypothesis that dexmedetomidine added to ropivacaine would safely enhance the duration of analgesia without adverse effects when compared with ropivacaine alone.We conducted a single-center, prospective, randomized, triple-blind, controlled trial of 62 patients undergoing elective shoulder surgery under general anesthesia with an interscalene block. Patients underwent ultrasound-guided interscalene blocks using either 12 mL of 0.5% ropivacaine or 0.5% ropivacaine plus 150-µg dexmedetomidine. The primary outcomes were self-reported duration of the nerve block and safety assessment (adverse effects and neurological sequelae). Data were analyzed in a blinded fashion.The median duration of the nerve block was 18 hours (95% confidence interval, 18–20) in the dexmedetomidine group and 14 hours (95% confidence interval, 14–16) in the ropivacaine group (P = 0.0001). Dexmedetomidine also lowered pain scores for the first 14 hours postoperatively and significantly hastened the time to sensory (P = 0.04) and motor (P = 0.002) block onset. Dexmedetomidine lowered heart rate but blood pressures were stable. Plasma levels of ropivacaine were not different between groups, and plasma dexmedetomidine levels were relatively low. There were no adverse events or neurological sequelae.Dexmedetomidine added to ropivacaine for interscalene blocks increased the duration of the nerve block and improved postoperative pain. These additional efficacy and safety data should encourage further study of peripheral perineural dexmedetomidine in humans.