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Introduction: Magnesium sulphate and dexmedetomidine can decrease the duration and intensity of postoperative pain due to their antinociceptive effects. Magnesium sulphate blocks N-methyl-D-aspartate receptor (NMDA) channel in a voltage dependant way, while dexmedetomidine acts on dorsal root neurons. Aim: To compare the analgesic efficacy and duration of postoperative analgesia after intraperitoneal instillation of magnesium sulphate and dexmedetomidine in laparoscopic cholecystectomy. Materials and Methods: The present study was a randomised clinical study, in which 90 patients of age 18-60 years, belonging to American Society of Anaesthesiologists (ASA) grade I or II were randomly selected and divided in three groups. Group M received magnesium sulphate 50 mg/kg with 0.25% bupivacaine 30 mL, group D received dexmedetomidine 1 µg/kg with 0.25% bupivacaine 30 mL, and group B received 0.25% of plain bupivacaine 30 mL. Pain was assessed using Visual Analog Scale (VAS) score as primary outcome, recorded at 0, 2, 4, 6, 8, 10, 12 and 24 hours after surgery. Time to rescue analgesia (VAS =4 or on demand) and patients satisfaction score were the secondary outcomes. All recorded data were analysed by statistical test (Analysis of Variance (ANOVA), post-hoc Tukey's HSD (Honest Significant Difference) test and Chi-square test). Results: The mean VAS score was 2.40±0.84, 2.57±0.78 and 2.88±0.92 in group M, group D and group B, respectively (p<0.05). The total analgesic requirement (Paracetamol) in first 24 hours postoperatively was lower in group M (1.73±0.58 gm), and group D (2.17±0.53 gm), than group B (2.70±0.47 gm). Highly satisfied patients in group M were 10, group D were 03, and none in group C. There were 14 highly dissatisfied patients in group B. The difference in the patient satisfaction score between groups was statistically significant (p=0.0002). Time to first rescue analgesia was highest in group M then group D. Conclusion: Intraperitoneal instillation of magnesium sulphate was found to be superior for postoperative analgesia in first 24 hours after laparoscopic cholecystectomy as reflected by a lower VAS score and longer duration of analgesia. [ABSTRACT FROM AUTHOR]