Background: Laryngoscopy and tracheal intubation are two of the most uncomfortable medical procedures that are connected to acute hemodynamic reactions that endure for at least ten minutes. When administering general anesthesia to a patient, particular care must be taken to keep the airway open. Aim and Objective: The aim of the study was to evaluate the efficacy of Esmolol and Dexmedetomidine in attenuating cardiovascular response to endotracheal intubation and its associated side effects. Methodology: The present Double Blinded Randomized Clinical Trial was conducted in the Department of Anesthesiology, Santosh Medical College and Hospital. Patients undergoing elective surgery under general anesthesia served as the subjects. Between the ages of 18 and 60, a sample of 60 patients with ASA grades I and II were divided into two groups of 30 individuals each. Result: Result showed that gender distribution was comparable in two groups with insignificant p value 0.26. Patients randomly divided into group D with mean age 31±11.82 years and group E with mean age 35.9±11.82 years which had no statistical significance. Maximum rise in HR, SBP, DBP was observed immediately after intubation which was way higher in Group E i.e. 90.07±3.62, 165.27±3.65, 93.4±4.46 respectively compared to Group D which was 84.8±2.3,128.33±4.96, 83.83±2.87 respectively which was significant with p≤ 0.5 . Comparison of MAP in the two groups revealed that MAP values were comparable at baseline and 15 minute interval (p≥.05). Conclusion: Dexmedetomidine (0.5μg/kg) was more effective than esmolol (0.5mg/kg) in attenuation of heart rate response to direct laryngoscopy and tracheal intubation. It concludes that Dexmedetomidine is better in reduction of post- operative nausea and vomiting.