Introduction <p>Septic shock is one of the most common causes of neonatal mortality. Dopamine and epinephrine are the two main drugs used in fluid refractory neonatal septic shock. However, there is lack of consensus on use of first line agent in neonates.</p> Study design <p>This randomized, open labeled, controlled trial was conducted with primary objective to compare the proportion of patients achieving reversal of shock at 60 min of starting either dopamine or epinephrine as first line inotrope in neonates with fluid refractory septic shock.</p> Results <p>More patients in the epinephrine group achieved reversal of shock than dopamine group (31 vs 25) but the difference was statistically not significant [<i>p</i> = 0.143, RR = 0.806 (95% CI 0.602,1.080)]. All-cause mortality was 87.5% (35/40) in the dopamine group and 85% (34/40) in the epinephrine group (34/40).</p> Conclusion <p>Dopamine and epinephrine show equivalent efficacy in reversal of shock at 60 min in neonates with septic shock.</p>