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Abstract Background Postoperative pain is one of the most common symptoms after surgery, which brings physical discomfort to patients. In addition, it may cause a series of complications, and even affect the long-term quality of life. The purpose of this prospective, randomized, double-blinded, controlled trial is to investigate the efficacy and safety of dexmedetomidine combined with sufentanil to attenuate postoperative pain in patients after laparoscopic nephrectomy. Methods Ninety patients undergoing laparoscopic nephrectomy were randomized into three groups: the control (sufentanil 0.02 μg/kg/h, Group C), sufentanil plus low dose of dexmedetomidine (0.02 μg/kg/h each, Group D1), and sufentanil plus high dose of dexmedetomidine (0.04 μg/kg/h, Group D2). The patient-controlled analgesia was programmed to deliver a bolus dose of 0.5 ml, followed by an infusion of 2 ml/h and a lockout time of 10 min. The primary goal was to calculate the cumulative amount of self-administered sufentanil; the secondary goals were to estimate pain intensity using the numerical rating scale (NRS), level of sedation, the first bowel movement, concerning adverse effects as well as duration of postoperative hospital stay. Results The total consumption of sufentanil in group D1 and D2 were significantly lower than in group C during the first 8 h after surgery (P 0.05) between group D1 and D2. Compared with group C, the NRS scores at rest during first 8 h after surgery were significantly lower in group D1 (P 0.05). The time to first flatus was shorter in group D1 compared with the control group (P

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