BACKGROUND: Intrathecal injection of analgesic agents sush as opioids, clonidine, ketamine and nalbuphine with a local anesthetic agent during spinal anesthesia for operation is an easy and convenient way to get postoperative analgesia. Intrathecal neostigmine causes an increased ACh concentration in CSF and also has an analgesic effect. This study was designed to examine its postoperative analgesic effect and adverse effects such as nausea/vomiting and urinary retention etc. METHODS: We divided 27 patients who were supposed to receive orthopedic surgery of lower extremities into 3 groups. The control group as injected with heavy bupivacaine 13 mg and normal saline and the N50 and N75 groups were injected with the same amount of bupivacaine combined with neostigmine 50 mcg and 75 mcg respectively. We examined total amount of fluid intake and side effects during operation, and time to first rescue analgesic medication, time to first urination, total applications of rescue analgesic agent, total number of urinary catheterizations for 24 hr after intrathecal injection, and adverse effects of intrathecal neostigmine in the ward. RESULTS: The N75 group showed a significantly longer analgesic duration compared with the control and N50 groups, but the incidence of urinary retention and number of urinary catheterizations increased in the N75 group significantly. Nausea/Vomiting significantly increased in N75 compared with control. Shivering was more common in N50. 2 patients who recieved neostigmine 75 mcg complained of chest discomforts suggesting myocardial ischemia in EKG taken in those episodes. CONCLUSIONS: Neostigmine 75 mcg has better analgesic effect but more frequent adverse effects than control or neostigmine 50 mcg. Therefore, we suggest using high doses of neostigmine cautiously and being aware of its side effects.