Background; This prospective ran­domized study was designed to com­pare the analgesic efficacy and safety of intrathecal (IT) neostigmine, IT morphine, versus IT bupivacaine in patients undergoing lower extremity orthopedic surgery. Methods : The study included sixty patients, 25 to 50 years old, ASA I and II, who were scheduled for lower extremity ortho­pedic surgery. According to the regi­men used for subarachnoid block, pa­tients were randomly assigned to one of three equal groups. The control group received 12.5 mg 0.5% bupiva­caine. The other groups received ei­ther 100 ug morphine (morphine group) or 25 ug neostigmine (neostigmine group), combined with 12.5 mg 0.5% bupivacaine. The onset
of sensory and motor blockade, dura­tion of analgesia, and the incidence of postoperative pain were recorded. The adequacy of postoperative anal­gesia was assessed using pain score. Patients were also observed for ad­verse effects such as hypotension, bradycardia, nausea and vomiting, pruritus, respiratory depression, dizzi­ness, and headache. Results : The onset of sensory and motor blockade did not differ significantly among the three groups. Compared with the con­trol group, both the morphine and ne­ostigmine groups were similarly asso­ciated with significant prolongation of the duration of analgesia (P <0.01), and significant reduction of both the incidence and degree (score) of postoperative pain (P <0.05). Among the studied groups,