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Intravenous (IV) dexmedetomidine is reported to prolong analgesia following peripheral nerve blocks. Popliteal sciatic nerve block provides effective postoperative analgesia, but some patients still experience severe pain during the early postoperative period. We aimed to evaluate the postoperative analgesic effects of IV dexmedetomidine versus propofol in patients undergoing foot surgeries under popliteal sciatic nerve block. Forty patients were enrolled and randomly assigned to receive either IV propofol (n = 20) or IV dexmedetomidine (n = 20) for intraoperative sedation. All the patients received continuous popliteal sciatic nerve block. The corresponding drug infusion rate was adjusted to achieve a modified observer's assessment of alertness/sedation score of 3 or 4. The primary outcome was postoperative cumulative opioid consumption during the first 24 h after surgery. Thirty-nine patients were analyzed. The median (interquartile ranges) postoperative cumulative opioid consumption during the first 24 h after surgery was significantly lower in the dexmedetomidine group (15 (7.5–16.9) mg) than in the propofol group (17.5 (15–25) mg) (p = 0.019). The time to first rescue analgesic request was significantly greater in the dexmedetomidine group than in the propofol group (11.8 ± 2.2 h vs. 10.0 ± 2.7 h, p = 0.030) without the prolonged motor blockade (p = 0.321). Intraoperative sedation with dexmedetomidine reduced postoperative opioid consumption and prolonged analgesic duration after a popliteal sciatic nerve block. [ABSTRACT FROM AUTHOR]