BACKGROUND: Intrathecal injection of analgesic agents such as opioids, clonidine, ketamine and nalbuphine with a local anesthetic produces analgesia in patients. Recently, the analgesic effect of intrathecal neostigmine has been investigated; however, the use of epidural neostigmine has not been investigated. The purpose of this study was to define the analgesic effectiveness and the side effects of epidural neostigmine. METHODS: Forty patients undergoing a total abdominal hysterectomy were divided into 4 groups. After intramuscular 0.1 mg/kg midazolam premedication, patients were randomized to receive epidural bupivacaine with saline (control group), 1 microgram/kg epidural neostigmine (Group I), 2 microgram/kg epidural neostigmine (Group II), or 3 microgram/kg epidural neostigmine (Group III) postoperatively. The concept of the visual analog scale, which consisted of a 10-cm line with 0 equaling "no pain at all" and 10 equaling "the worst possible pain" was introduced. Pain was assessed by using the visual analog scale at 1, 3, 6, 9, 12, and 24 h postoperatively, and intramuscular 90 mg diclofenac was available at the patient's request. RESULTS: The visual analog scale score at first rescue analgesic and the incidence of adverse effects were similar among neostigmine groups. The analgesic consumption in 24 hours and the pain visual analog scale score at 3 h, 12 h, and 24 h were significantly decreased in neostigmine groups compared with control groups. CONCLUSIONS: Epidural neostigmine coadministered with bupivacaine produces a dose-independent analgesic effect compared to the control group and a reduction in postoperative rescue analgesic consumption without increasing the incidence of adverse effects.