AbstractIntroduction: Direct laryngoscopy and endotracheal intubation induces cardiovascular stress response which in turn leads to increase in plasma catecholamine concentration and rise in blood pressure and heart rate. Fentanyl is a popular opioid used to attenuate a presser response to laryngoscopy and intubation. In this study, we compared two different doses of fentanyl 2 mcg/kg and 4 mcg/kg to asses maximum effectiveness and safety to prevent stress response during laryngoscopy and intubation. Methods: In this prospective comparative clinical study, 30 patients aged 18 to 50 years of ASA physical status I and II, scheduled for elective surgery under general anesthesia requiring endo tracheal intubation. Patients were randomized into two groups of 15 patients each: Group A: Received 2 μg/kg of fentanyl IV 5 minutes before induction. Group B: Received 4 μg/kg of fentanyl IV 5 minutes before induction. All groups were assessed for hemodynamic changes after premedication, during laryngoscopy and intubation, after intubation at 1, 3, 5 and 10 minutes, postoperative sedation and postoperative side effects. Results: Fentanyl in doses of 4 mcg/kg was effective in complete prevention of hemodynamic stress response during laryngoscopy and intubation. However, 4 mcg/kg of fentanyl produced a 15–20% decrease in hemodynamic variables from baseline compared to 5–10% with 2 mcg/kg of fentanyl. Conclusion: Fentanyl in dose of 4 μg/kg five minutes before induction is the most appropriate dose in terms of efficacy and safety for preventing hemodynamic stress response during laryngoscopy and intubation.