Objective: Vasoconstrictors are one of the therapeutic modalities in the treatment of septic shock. In the present study, we have compared the effects of dopamine and norepinephrine in the treatment of septic shock with pre-defined end-points and continuous non-invasive cardiac output monitoring using impedance cardiography. Design: Randomized controlled trial. Settings: Sixteen-bedded mixed intensive care unit of a tertiary care teaching institution. Materials and Methods: The study included 50 consecutive patients presenting with septic shock and divided randomly into two groups with 25 patients in each group. Group I patients were treated with dopamine and those in Group II were treated with norepinephrine. They were optimized with fluid resuscitation upto CVP>10 cm of H ₂ O, packed red cells transfusion upto hematocrit >30, oxygenation and ventilation upto PaO ₂ >60 mmHg before the inotropes were started. The goal of therapy was to achieve and maintain for six hours, all of the following: (1) SBP >90 mm Hg, (2) SVRI >1100 dynes.s/cm ⁵ m ², (3) Cardiac Index >4.0L/min/m ², (4) IDO ₂ >550 ml/min/m ₂ and (5) IVO ₂ >150 ml/min/m ². Measurements: The demographic data, baseline parameters and post-treatment parameters were statistically analyzed by using t-test. Results: The post-treatment parameters were statistically significant showing the superiority of norepinephrine over dopamine in optimization of hemodynamics and patient survival. Significant improvement in systolic blood pressure, heart rate, cardiac index, SVRI, IVO ₂ and urine output were found in norepinephrine group than the dopamine group. Dopamine showed a response in 10 out of 25 patients up to a maximum dose of 25 mcg/kg/min while with norepinephrine, 19 patients responded up to a maximum dose of 2.5 mcg/kg/min The hemodynamic parameters were preserved in norepinephrine group with better preservation of organ perfusion and oxygen utilization with maintenance of splanchnic and renal blood flow as evidenced by significant increase in O2 uptake and urine flow. Conclusion: Norepinephrine was more useful in reversing the hemodynamic and metabolic abnormalities of septic shock compared to dopamine at the doses tested.