Pain is a complex medical problem that its inadequate postoperative control has adverse effects on patients’ physiological, metabolic and mental status. Adding new supplements will lead to an increased duration of analgesia. The purpose of this study was to compare the addition of neostigmine and ketamine to bupivacaine 0.25% for epidural analgesia increasing duration of postoperative analgesia. In this double blind clinical trial, 90 patients over 50 years candidated for elective hip surgery with ASA class I, II were randomly divided to three groups: neostigmine, ketamine and control groups. All patients received epidural with bupivacaine 0.25% by 2cc/segment. Furthermore, 60 micrograms neostigmine was added in first group and 40 mg ketamine was used for group II. Level of postoperative pain based on VAS and duration of analgesia and amount of analgesic was determined and compared across the three groups. The mean of pain score at 6 and 12 hours after surgery was significantly lower in the ketamine group than the other groups and in neostigmine group was less than placebo (P ≤ 0.01). The mean of duration of postoperative analgesia in the ketamine group was significantly higher than the other groups and in neostigmine group was more than placebo (P ≤ 0.01). The mean dose of analgesic (pethedin) was the least in the ketamine group (P ≤ 0.001). Neostigmine and ketamine with bupivacaine 0.25% for epidural anesthesia increased the duration of analgesia during the postoperative period and reduced analgesic consumption that about ketamine was more than neostigmine.