Introduction: The objective of the study was to assess and compare the analgesic effectiveness and safety profiles of pethidine in relieving pain experienced post major surgical procedures. Material And Methods: A prospective interventional investigation was carried out on a cohort of 71 patients who underwent a significant surgical procedure. In this study, a total of 71 patients were administered intramuscular medication for a duration of 48 hours following surgery. Specifically, 36 individuals were treated with placebo dosages of 3 CC administered at 6-hour intervals, whereas the remaining 35 received 100 mg doses of pethidine at the same frequency. The present study aimed to evaluate and compare the analgesic efficiency and safety of placebo and pethidine. The aforementioned evaluation was performed at various time intervals of 1, 6, 12-, 24-, 32-, and 48-hours post-administration of the respective drugs. The efficacy of analgesics was evaluated through the utilization of both the Visual Analogue Scale (VAS) and Verbal Rating Scale (VRS). Results: The present study demonstrated the equianalgesic efficacy between placebo and Pethidine as determined by both Visual Analogue Scale (VAS) scores at 12 and 48 hours, and Verbal Rating Scale (VRS) scores at 1 and 48 hours during the postoperative period. During alternative observation periods, it was observed that pethidine demonstrated superior analgesic properties when compared to ketorolac. Conclusion: Pethidine demonstrated a higher degree of efficacy as an analgesic agent in comparison to ketorolac. Additional investigations, comprising a double-blind randomized trial, have been proposed to authenticate the findings presented in the current undertaking.