Spinal anesthesia with bupivacaine is routinely administered for lower limb and perianal surgery. The ensuing nerve blockage is sufficient to provide adequate motor blockage, which facilitates the surgeon’s work and also provides effective pain relief during the initial postoperative period. In order to maximize post-operative analgesia, a number of adjutants have been added to local spinal anesthetics. Intrathecal supplements for post-operative pain relief are intriguing as they eliminate the need for intravenous and intramuscular analgesics and their associated complications. The objective of this study is to compare the intensity and duration of post-operative pain relief using intrathecal ketamine and midazolam with bupivacaine in patients undergoing lower limb and perianal surgery. This prospective, open label, parallel assignment, randomized, single-center trial, included eighty patients, who admitted for lower limb and perianal surgeries to the M.S. Ramaiah Medical College and Hospital, University- affiliated tertiary care center in Bangalore, India, were studied for 6 months. ASA (American Society of Anesthesiology) grade I and II patients between the ages of 20 and 60 years were included in this study. The onsets of action, intra-operative vital signs, postoperative vital signs, pain assessment by visual analogue scale, and post- operative analgesia time were recorded. A significantly higher VAS score were seen in group I (Ketamine). Postoperative analgesia was supplemented in all patients in group I at a mean duration of 482 ± 68.22 minutes and in group II at a mean duration of 645 61.28 minutes. The difference in mean post-operative supplemental analgesic time between the 2 groups was very highly significant (p < 0.001). Intrathecal midazolam with bupivacaine provides very good and prolonged post-operative analgesia compare to intrathecal ketamine with bupivacaine.