Background: Endotracheal intubation and laryngoscopy are often associated with increased sympathetic response due to stimulation of laryngeal and tracheal sensory receptors. This can be harmful especially in patients who have cardiac issues, hypertension, etc. and can be associated with increased morbidity and mortality. Attenuation of pressor response can prevent sympathetic stimulation. Aim: To evaluate and compare oral Clonidine and intravenous Esmolol for attenuation of pressor response during laryngoscopy and endotracheal intubation. Materials and methods: 60 patients were divided into two groups after satisfying the inclusion and exclusion criteria. Group-A received clonidine orally at a dose of 150 mcg, around 75–90 minutes before elective surgery. Group-B received intravenous esmolol at a dose of 1.5mg/kg, 2 minutes prior to laryngoscopy. HR, SBP, DBP, MAP were recorded at time of shifting to operation theatre (T0), subsequent to administration of premedications (T1), prior to laryngoscopy (T2), subsequent to intubation (T3), at 1 minute (T4), 3 minutes (T5), 5 minutes (T6) and 10 minutes (T7) subsequent to intubation. Side effects if any were recorded. Results: There was significant suppression of HR, SBP, DBP and MAP at T3, T4, T5, T6 and T7 in Group B that received Intravenous esmolol. There were no serious adverse events in either of the group. Conclusion: Esmolol can be an effective pharmacological agent that can be used for attenuation of pressor response during laryngoscopy and endotracheal intubation. We suggest conducting similar study in patients with significant co-morbidities for a more comprehensive analysis.