OBJECTIVE We compared efficacy of dopamine and epinephrine as first-line vasoactive therapy in achieving resolution of shock in fluid-refractory hypotensive cold septic shock. DESIGN Double-blind, pilot, randomized controlled study. SETTING Pediatric emergency and ICU of a tertiary care teaching hospital. PATIENTS Consecutive children 3 months to 12 years old, with fluid-refractory hypotensive septic shock, were enrolled between July 2013 and December 2014. INTERVENTION Enrolled children were randomized to receive either dopamine (in incremental doses, 10 to 15 to 20 μg/kg/min) or epinephrine (0.1 to 0.2 to 0.3 μg/kg/min) till end points of resolution of shock were achieved. After reaching maximum doses of test drugs, open-label vasoactive was started as per discretion of treating team. Primary outcome was resolution of shock within first hour of resuscitation. The study was registered (CTRI/2014/02/004393) and was approved by institute ethics committee. MEASUREMENTS AND MAIN RESULTS We enrolled 29 children in epinephrine group and 31 in dopamine group. Resolution of shock within first hour was achieved in greater proportion of children receiving epinephrine (n = 12; 41%) than dopamine (n = 4; 13%) (odds ratio, 4.8; 95% CI, 1.3-17.2; p = 0.019); the trend persisted even at 6 hours (48.3% vs 29%; p = 0.184). Children in epinephrine group had lower Sequential Organ Function Assessment score on day 3 (8 vs 12; p = 0.05) and more organ failure-free days (24 vs 20 d; p = 0.022). No significant difference in adverse events (16.1% vs 13.8%; p = 0.80) and mortality (58.1% vs 48.3%; p = 0.605) was observed between the two groups. CONCLUSION Epinephrine is more effective than dopamine in achieving resolution of fluid-refractory hypotensive cold shock within the first hour of resuscitation and improving organ functions.