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We examined data from a contemporary cohort of extreme prematurity (EP) infants admitted to an all-referral Children's Hospital neonatal intensive care unit (NICU) to determine whether prophylactic indomethacin (PI) may continue to benefit these patients.An observational study utilizing the small baby ICU data registry that was queried for all EP infants admitted between 2005 and 2014 with documentation of PI use (671 total EP infants; 141 (21%) did not receive PI (control); 530 (79%) received PI (PI). This cohort of EP infants was born at outside hospitals and transferred to our level IV NICU with a mean age on admission of 13 days, well after the PI would have been administered.No difference existed between the control and PI groups in gestational age, birth weight, severity of illness, other in-hospital outcomes or developmental delay. PI infants had a significantly lower mortality rate (P = 0.0004), lower relative risk (RR) for mortality 0.52 (95% confidence interval (CI) 0.37 to 0.73, P = 0.0001) and lower RR of developing the combined outcome of death or bronchopulmonary dysplasia (RR 0.91, 95% CI 0.85 to 0.98, P = 0.012) when compared with the control group. Notably, there was no significant effect of PI on incidence of severe intraventricular hemorrhage or patent ductus arteriosus ligation.PI administration was associated with improved survival in EP infants referred to a level IV Children's Hospital NICU.