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Background: Although laparoscopic operations are minimally invasive, many patients report moderate-to-severe pain in the early postoperative period, which is multifactorial and requires multimodal analgesia to relieve it. Pain after laparoscopic surgery is caused by three mechanisms: parietal, visceral, and shoulder pain. As a result, numerous studies were done to develop methods for good postoperative pain control. Aim of the Work: This study aims to compare the efficacy of intravenous dexmedetomidine versus intraperitoneal bupivacaine-dexmedetomidine for postoperative analgesia after laparoscopic cholecystectomy. Patients and Methods: The study was conducted on 52 patients aged 21 to 60 years, of American Society of Anesthesiologists (ASA) class I or II scheduled for elective laparoscopic cholecystectomy under general anesthesia in Ain Shams University Hospitals after approval of the medical ethical committee. They were allocated to two groups of 26 patients each: Group A: (n=26): Patients received an intravenous infusion of 50 ml of normal saline containing dexmedetomidine 1lg/kg over 10 minutes after removal of the gall bladder, Group B: (n=26): Patients received intraperitoneal instillation of dexmedetomidine 1lg/kg plus 40 ml of bupivacaine 0.25%. Results: There was a statistically significant difference between both groups regarding pain control and postoperative analgesic requirements while there was no significant difference between both groups regarding the demographic data and postoperative side effects (hypotension, bradycardia, nausea, and vomiting). Both intravenous dexmedetomidine and intraperitoneal bupivacaine-dexmedetomidine were effective for postoperative pain control after laparoscopic cholecystectomy but the intraperitoneal route provided a longer duration of analgesia and the lower postoperative analgesic consumption Conclusion: The present study concluded that patients who received intraperitoneal administration of bupivacaine-dexmedetomidine had less VAS with a longer duration of analgesia and lower postoperative analgesic consumption than those who received intravenous dexmedetomidine. [ABSTRACT FROM AUTHOR]