Background: Tapentadol having both mu-opioid receptor agonist and norepinephrine reuptake inhibitor characteristics has better GI profile and analgesic efficacy in acute and chronic including neuropathic pains. Post operative pain using tapentadol nasal spray with quicker recovery helps in minimizing the amount of time required for patient to be on bed rest, reduced hospital day, hospital expenditure and overall patient satisfaction. Objectives: We conducted this study to compare the efficacy of Tapentadol Nasal Spray and Diclofenac IV in the Post operative patients of Laparoscopic Cholecystectomy by using VAS (Visual Analogue Scale), to compare tapentadol and diclofenac in terms of safety of administration and to study the cost effectiveness. Methods: Using randomized, prospective study design, half of post-operative cases were prescribed tapentadol nasal spray and were assigned Group A. The second half of the postoperative cases received intravenous diclofenac and were assigned Group B. Scheduled dose of tapentadol nasal spray was 22.5 mg in each nostril and for intravenous diclofenac dose was 75 mg. Results: It was observed that the mean pain score in the subjects of the tapentadol nasal spray group was comparatively lower than intravenous diclofenac group by VAS (p<0.05). Conclusion: Tapentadol nasal spray at 22.5 mg in each nostril was found to be effective in managing the post operative pain with minimal side effects.