Background: Tracheal extubation is associated with a 10-30% increase in arterial pressure and heart rate that could be detrimental in patients with hypertension, ischemic heart disease, and cerebrovascular disease. A reliable technique for rapid & smooth extubation with stable hemodynamics is still not fully evolved. Aims: To compare the effect of intravenous magnesium sulphate and esmolol for attenuating hemodynamic response to extubation after general anesthesia. Setting and Design: Prospective, randomized, double blind study conducted at tertiary care hospital. Methods: Sixty adult subjects undergoing major surgery were randomly divided into 2 groups. Group M received magnesium sulphate 40 mg/kg & Group E received esmolol 0.6 mg/kg IV infusion over 5 minutes before extubation. Heart rate, systolic & diastolic blood pressure, mean arterial pressure, rate pressure product, pain score & sedation score were compared from extubation till 15 minutes after extubation. Statistical Analysis: Students 't' test used for continuous variables & Chi Square test for categorical data. Results: 21.82% fall in heart rate was observed in group M with a plateau at 10 -15 minutes compared to 37.07% in group E with a peak at 15 minutes (p=0.0150). Fall in Systolic blood pressure was 18.86% in group M & 21.15% in group E (p=0.4298). Rate pressure product was significantly lower in group E (50.40%) than group M (36.66%). Postoperative pain score was significantly less in group M compared to group E (p<0.0001). Conclusion:Magnesium sulphate provides better hemodynamic stability with postoperative analgesia compared to esmolol when used for attenuating hemodynamic response to extubation.