Introduction: The stress response to laryngoscopy and endotracheal intubation activates the sympathetic nervous system, which may increase myocardial oxygen demand by increasing heart rate and arterial blood pressure. Activation of the sympathetic nervous system may also cause coronary artery vasoconstriction reducing the supply of oxygen to the myocardium, which in turn would pre-dispose to myocardial ischemia. Aims: To study the effectiveness of Lignocaine 2 mg/kg and Esmolol 200 mg and to ascertain the superiority of Esmolol over lignocaine or vice versa in suppressing sympathetic response. Materials and Methods: A clinical comparative study of attenuation of sympathetic response to laryngoscopy and intubation was done in 150 patients posted for elective surgeries under general anesthesia with endotracheal intubation for all the patients. Patients were allocated randomly to the Three Groups, Group 1 (Control), Group II (Lignocaine) and Group III (Esmolol) 50 patients in each group. Results: In patients with no drugs to attenuate the sympathetic responses to laryngoscopy and intubation the maximum rises in heart rate, systolic, diastolic and mean arterial blood pressures were statistically and clinically very highly significant and can be detrimental in high risk patients. Lignocaine significantly attenuates the sympathetic responses to laryngoscopy and tracheal intubation. Esmolol also very significantly attenuates the sympathetic responses. Conclusion: Esmolol is more efficient than lignocaine in attenuating the sympathetic responses to laryngoscopy and intubation. Esmolol at a bolus dose of 200 mg I.V. administered. 3 minutes before laryngoscopy and intubation can be recommended to attenuate the sympathetic responses due to laryngoscopy and intubation.