Introduction The creation of pneumoperitoneum leads to increased mean arterial pressure and systemic vascular resistance as a result of stimulation of the sympathetic system leading to increased release of catecholamines and vasopressin. In order to prevent these hemodynamic changes, various pharmacological agents like clonidine, esmolol, or dexmedetomidine are used. Hence, there is need for this study. Materials and methods A total of 60 patients were randomized into two equal groups: group D—dexmedetomidine was administered as loading dose 1 µg/kg administered slowly over 15 minutes before induction followed by maintenance infusion of 0.5 µg/kg/hour throughout the period of pneumoperitoneum. Group E—esmolol was administered as loading dose at 1 mg/kg administered slowly over 5 minutes before induction followed by maintenance infusion of 0.5 mg/kg/hour throughout the period of pneumoperitoneum. Intra-abdominal pressure was maintained at 12 to 14 mm Hg throughout the procedure. The infusions were discontinued immediately after the release of pneumoperitoneum. Heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure were recorded at frequent intervals as per the pro forma. Data were analyzed using appropriate statistical tests. Results and conclusions As compared with esmolol, dexmedetomidine is more effective for attenuation of the pressor responses to pneumoperitoneum and thus achieving hemodynamic stability during laparoscopic surgeries (p < 0.05). How to cite this article Gupta P, Agrawal M, Jethava D, Jethava DD. A Comparison of the Effect of Dexmedetomidine and Esmolol in Attenuating Stress Responses during Laparoscopic Surgeries. J Mahatma Gandhi Univ Med Sci Tech 2017;2(3):151-156.