Background:Unrelieved post-operative pain may result in the physical suffering as well as multiple physiological and the psychological consequences, which may adversely affect the peri-operative outcome and contribute to increase the length of stay in hospital.Objectives:We designed this study to evaluate the effect of IV Paracetamol and Dexmedetomidine as multimodal analgesic technique on post-operative analgesia and to reduce the consumption of the systemic opioid and its adverse effects in cases of laparoscopic cholecystectomy.Materials and Methods:Eighty consenting, American society of Anesthesiologist-physical status-I (ASA-PS-I), female patients, aged 19-60 year was randomly assigned to one of the following two groups: Group P (n = 40) received IV 1 g Paracetamol infusion over 10 min pre-operatively and 6 hourly thereafter and Group D (n = 40) received IV Dexmedetomidine 1 μg/kg bolus over 10 min pre-operatively and 0.2-0.4 μg/kg/h thereafter for 24 h. Peri-operative hemodynamic variables, post-operative pain scores, and the need for rescue analgesics were recorded and compared.Results:Profiles of intra-operative hemodynamic changes were similar in both groups in respect to heart rate (HR), diastolic blood pressure, mean arterial pressure except in the systolic blood pressure where Dexmedetomidine significantly reduced it in compare to Paracetamol (P = 0.014). Post-operatively 4th h and 24th h changes in mean HR between two groups was a statistically significant (P < 0.05). Visual analog scale scores were significantly lower in the Group P compared with Group D at 8th, 16th, and 24th h (P < 0.001). Sedation score were statistically higher in the Group D compared with the Group P at post-operative 4th, 8th, 16th, and 24th h (P < 0.006).Conclusion:Adjunctive use of both Paracetamol and Dexmedetomidine infusion reduced opioid use. However, Paracetamol peri-operatively provides adequate analgesia with the less sedation whereas Dexmedetomidine provides analgesia and co-operative sedation.