Objective. Our objective is to investigate the efficacy and safety of intraperitoneal dexmedetomidine (Dex) combined with bupivacaine in patients undergoing laparoscopic colorectal cancer surgery. Design. Randomized double-blind study. Setting. Academic medical center. Patients and methods. Forty-five patients scheduled for laparoscopic colorectal cancer surgery were randomly assigned for intraperitoneal administration of 50 mL saline (control group; GI, n515), 50 mL bupivacaine 0.25% (125 mg; GII, n515), or 50 mL bupivacaine 0.25% (125 mg) 11 lg/kg Dex (GIII, n515). Patients were assessed during the first 24 hours postoperatively for hemodynamics, visual analogue scale (VAS), time to first request of analgesia, total analgesic consumption, shoulder pain, and side effects. Results. A significant reduction was observed in VAS in GIII at base line, 2, 4, and 24 hours postoperatively in comparison to GI and GII (P 0.05). The time to first analgesic requirement was significantly prolonged in GIII (P 0.05). The mean total consumption of rescue analgesia was significantly reduced in GIII. Conclusion. We conclude that intraperitoneal administration of Dex 1 lg/kg combined with bupivacaine improves the quality and the duration of postoperative analgesia and provides an analgesic sparing effect compared to bupivacaine alone without significant adverse effects in patients undergoing laparoscopic colorectal cancer surgery.