Both central sensitization after peripheral tissue injury and the development of opiate tolerance involve activation of N-methyl-d-aspartate receptors. In this double-blinded, randomized study, we investigated the preemptive versus postincisional effects of dextromethorphan and ketamine, an N-methyl-D-aspartate receptor antagonists, on postoperative pain management. 75 ASA I and II patients undergoing emergency abdominal surgeries were randomly allocated to five equally sized groups. The preincisional dextromethorphan group: patients received (120 mg) IM 30 min before skin incision and a placebo (isotonic saline) 30 min before the end of surgery. The preincisional ketamine group: patients received (120 mg) IM 30 min before skin incision and a placebo (isotonic saline) 30 min before the end of surgery. The postincisional dextromethorphan group: received the same dose(120 mg IM) 30 min before the end of surgery and a placebo 30 min before skin incision. Postincisional ketamine group: received the same dose (120 mg IM) 30 min before the end of surgery and a placebo 30 min before skin incision. The and the Control group received a placebo both 30 min before skin incision and 30 min before the end of surgery. A standard general anesthetic technique including fentanyl, propofol, isoflurane, and atracurium was used. Postoperative meperidine patient-controlled analgesia (PCA) was used. In conclusion, preincisional IM 120 mg dextromethorphan compared with the other four groups significantly reduced postoperative morphine consumption; postincisional dextromethorpan, preincisional and postincisional ketamine and the control group significantly reduced postoperative meperidine consumption.