We designed this study to evaluate the postoperative analgesic efficacy and safety of intrathecal (i.t.) neostigmine, i.t. morphine, and their combination in patients undergoing cesarean section under spinal anesthesia. Seventy-nine term parturients were randomly divided into four groups to receive isotonic sodium chloride solution 0.2 mL, neostigmine 25 microg, morphine 100 microg, or the combination of i.t. neostigmine 12.5 microg and morphine 50 microg with i.t. 0.5% hyperbaric bupivacaine 12 mg. There were no significant differences among the four groups with regard to spinal anesthesia, maternal blood pressure and heart rate, or fetal status. Postoperative analgesia was provided by i.v. patient-controlled analgesia (PCA) using fentanyl and ketorolac. Compared with the saline group, the time to first PCA use was significantly longer in the neostigmine group (P < 0.001), with lower 24-h analgesic consumption (P < 0.001). Nausea and vomiting were the most common side effects of i.t. neostigmine (73.7%). Analgesic effectiveness was similar between the neostigmine and morphine groups. Compared with the neostigmine group, the combination group had significantly prolonged analgesic effect and reduced 24-h PCA consumption (P < 0.05) with less severity of nausea and vomiting (P = 0.058). Compared with the morphine group, the combination group tended to have prolonged times to first PCA use (P = 0.054) with a lower incidence of pruritus (P < 0.03). CONCLUSIONS Intrathecal (i.t.) neostigmine 25 microg produced postoperative analgesia for cesarean section similar to that of i.t. morphine 100 microg, but with a high incidence of nausea and vomiting. The combination of i.t. neostigmine 12.5 microg and i.t. morphine 50 microg may produce better postoperative analgesia with fewer side effects than i.t. neostigmine 25 microg or i.t. morphine 100 microg alone.