We performed a randomized, prospective, controlled trial in 54 patients, to compare norepinephrine and phenylephrine in the management of dopamine resistant septic shock. Patients were randomly allocated to receive either norepinephrine or phenylephrine infusion titrated to achieve a predefined haemodynamic and tissue perfusion targets for continuous 6 hrs as per protocol of our study. All the parameters were recorded every 30 min and increment in dose of studied drug was done in the specified dose range if targets were not achieved. Data from pulmonary arterial and hepatic vein catheterization, thermodilution catheter, blood gas analysis, blood lactate levels, invasive blood pressure, and oxygen transport variables were compared with baseline values after achieving the targets of therapy. No difference was observed in any of the investigated parameters except for statistically significant reduction of heart rate (HR) and increase in stroke volume index (SVI) by phenylephrine. We concluded that both drugs are comparable in reversing hemodynamic and metabolic abnormalities of sepsis patients, with an additional benefit of decrease in HR and improvement in SVI by phenylephrine.