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Dexmedetomidine has sedative, sympatholytic, analgesic, and anti-inflammatory effects. We investigated the effects of intraoperative dexmedetomidine infusion without a loading dose in the prevention of pain and inflammation after laparoscopic hysterectomy. In this study, 100 patients undergoing laparoscopic hysterectomy under desflurane anesthesia were randomized to receive either 0.9% saline or dexmedetomidine (0.4 μg/kg/h) after induction to trocar removal. The primary endpoints were postoperative pain and inflammatory response presented by the level of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-10, and C-reactive protein (CRP). The secondary endpoints were hemodynamics during the anesthesia and surgery and postoperative nausea and vomiting. Postoperative pain was decreased in the dexmedetomidine group for every time point, and post-anesthesia care unit (PACU) rescue fentanyl doses were decreased in the dexmedetomidine group. The inflammatory response representing TNF-α, IL-6, IL-10, and CRP were similar across the two groups. Postoperative nausea and vomiting from PACU discharge to 24 h post-surgery were reduced in the dexmedetomidine group. During anesthesia and surgery, the patient's heart rate was maintained lower in the dexmedetomidine-receiving group. Dexmedetomidine of 0.4 μg/kg/h given as an intraoperative infusion significantly reduced postoperative pain but did not reduce the inflammatory responses in patients undergoing laparoscopic hysterectomy.