BACKGROUND: Evidence has accumulated that tramadol hydrochloride can produce relief of moderate to severe pain across the range of acute and chronic pain states by combining a synergistically weak opioid and a monoaminergically mediated antinociceptive mechanism. Neostigmine can produce antinociceptive effects by interacting with muscarine receptors in peripheral tissues. This study was designed to determine whether intraarticular tramadol results in better analgesic effect and whether tramadol and neostigmine would provide superior analgesia to tramadol alone, after knee arthroscopic surgery. METHODS: Forty-five ASA class 1 or 2 patients undergoing arthroscopic knee surgery were randomly allocated to three treatment groups. All patients received general anesthesia with nitrous oxide, O2 and inhalational agents. When the surgical procedure was completed, the study drug was injected into the patient's knee joint through the arthroscope. Patients in group 1 (n = 15) received 30 ml of 0.5% mepivacaine; patients in group 2 (n = 15) received tramadol 50 mg and 30 ml of 0.5% mepivacaine; patients in group 3 (n = 15) received a combination of tramadol 50 mg, neostigmine 100 micro gram and 30 ml of 0.5% mepivacaine. Postoperative pain was assessed using the visual analogue scale (VAS) at 1, 2, 4, 6, 12 and 24 hours after the intraarticular injection. RESULTS: There were no significant differences among the three groups in the 1 to 2 hour postoperative period and groups 2 and 3 showed significantly lower VAS score than group 1 from 4 to 24 hours postoperatively. CONCLUSIONS: It is concluded that after knee arthroscopy, intraarticular injection of tramadol had a good analgesic effect, whereas neostigmine added to tramadol did not show superior analgesic effects over tramadol alone.