OBJECTIVE: To compare early hydrocortisone (initiated along with vasoactive therapy) vs. placebo for all-cause mortality within next 14 days among neonates with fluid-refractory shock. STUDY DESIGN: Neonates with fluid-refractory shock were randomly assigned to receive hydrocortisone or saline placebo alongside vasoactive drugs. If they developed catecholamine-resistant shock, the study drug was replaced with open-label hydrocortisone. RESULT: Eighty-four neonates were randomized (early hydrocortisone=43 and placebo=41). Median gestational age of our cohort (n = 84) was 30.3 weeks [interquartile range (IQR): 27.7, 32.5] and median birth weight was 1148 grams (IQR: 860, 1419). The 14-day all-cause mortality was comparable between early hydrocortisone and placebo groups [OR 0.53 (95% CI 0.19, 1.52)]. Both groups had similar duration of vasoactive drugs and vasoactive-inotrope scores, incidence of adverse effects of hydrocortisone and incidence of medium-term complications. CONCLUSION: We did not observe a significant reduction in 14-day mortality with early hydrocortisone compared to placebo in fluid-refractory neonatal shock.