Background: The choices of premedication and anesthetic techniques are able to influence the neurohormonal stress response by modulating the pathophysiological pathways. Various pharmacological agents like nitroglycerine, beta blocker, and opioids were used to decrease surgical stress of laparoscopic procedures to improve outcome, with their own limitations.  Objective: It was to compare the effect of opioid-free (using dexmedetomidine and propofol) and opioid-based (using fentanyl and propofol) TIVA techniques on hemodynamic stability, sedation postoperative pain intensity and the incidence of side effects in patients scheduled for LC. Patients and Methods: Eighty patients who were scheduled for elective laparoscopic cholecystectomy were included in this study. Before induction of anesthesia, patients were randomly divided into two equal groups: (40 each). Dexmedetomidine group(Non-opioid group) received dexmedetomidine (1 µg/kg) over 10 minutes before induction of anesthesia followed by continuous infusion of 0.5 µg/kg/hr. till the end of surgery and Fentanyl group (Opioid group) received fentanyl (1.0 µg/kg) over 10 minutes before induction of anesthesia followed by continuous infusion of 0.4 µg/kg/hr. till the end of surgery. Results: The results of the present study showed that there were no significant differences between the two groups regarding HR and MAP except after loading dose of the studied drugs, after intubation, after pneumoperitoneum, 15 min, 30 min, 45 min, and 60 min after induction where it was lower in dexmedetomidine group than fentanyl group. There were no significant differences between two groups regarding intraoperative SPO2, postoperative SPO2 and blood glucose level (mg/dl). Conclusion: This study concluded that dexmedetomidine is better than fentanyl for patients who undergo elective laparoscopic cholecystectomy due to perioperative maintaining of hemodynamic stability, decrease dosages of postoperative analgesics, prolong the duration of postoperative analgesia and decrease postoperative nausea and vomiting.