BACKGROUND: Intrathecal (IT) neostigmine produces analgesia in animal and human. This study was designed to evaluate the efficacy and safety of IT neostigmine for post-cesarean section analgesia. METHODS: Forty-five women undergoing cesarean section under spinal anesthesia were randomly assigned into 3 groups to receive; normal saline 0.2 ml, or neostigmine 12.5 microgram, or neostigmine 25 microgram intrathecally with 0.5% hyperbaric bupivacaine 12 mg. Degrees of sensory and motor blocks, maternal hemodynamic changes, and side effects were recorded. Apgar scores and umbilical vein blood gas analysis (UVBGA) were checked for evaluation of fetal status. Postoperative analgesia was provided by intravenous patient-controlled analgesia (PCA) using fentanyl 500 microgram and ketorolac 150 mg in 100 ml. Pain scores with 10-cm visual analogue scale (VAS), time to first PCA use, cumulative PCA consumptions, and side effects were assessed at 1, 2, 4, 8, 12, 24, and 48 hr after IT injection. RESULTS: There were no significant differences among the three groups in characteristics of spinal anesthesia, maternal blood pressure and heart rate, Apgar scores, and UVBGA data. Compared to saline group, IT neostigmine significantly prolonged time to first PCA use and decreased 24 hr- and 48 hr-PCA consumptions (P<0.05). Pain scores in neostigmine groups were significantly lower than those in saline group for first 4 hr after which there were no differences among the three groups. There were significantly higher incidences of nausea and vomiting in neostigmine groups than in saline group. CONCLUSIONS: These data indicate that IT neostigmine can be an alternative postoperative analgesic without adverse fetal effects for cesarean section. However, high incidence of nausea and vomiting seem to limit its clinical usefulness. Further studies are necessary to enhance its analgesic effects and to decrease its adverse effects.