The aim of this study was to compare the analgesic efficacy of diclofenac sodium, ketorolac, tramadol individually and their combination after laparoscopic cholecystectomy. Total 150 subjects who met the inclusion and exclusion criteria were randomly (lottery method) divided into five groups to receive respective treatment. Pain score was measured after 1, 2, 4, 6, 12, 24 and 48 hours after surgery through visual analogue scale. The data was statistically analyzed through SPSS (version 20.0). It is concluded on the basis of collected results that a combination of Non-Steroidal Anti-inflammatory Drugs and Opioid derivatives is much superior to achieve effective pain control than either of the drug alone. Furthermore, ketorolac and tramadol combination provided more efficient pain control than diclofenac sodium and tramadol combination. This effective pain control is associated with short hospital stay which will cause less economic burden for patients. So, we may recommend that Non-Steroidal Anti-inflammatory Drugs (ketorolac) and opioids (tramadol) combination should be used for effectual pain control after laparoscopic cholecystectomy.