BackgroundNecrotizing enterocolitis (NEC) is a major cause for morbidity and mortality among newborn infants. Chorioamnionitis is a perinatal complication that is associated with preterm delivery. Few reports have studied chorioamnionitis as a possible risk factor for NEC. Further investigation is needed to fully understand this association. ObjectiveTo examine the association of chorioamnionitis with NEC in newborn infants. MethodsWe used National Inpatient Sample (NIS) datasets produced by the federal Healthcare Cost and Utilization Project (HCUP). We identified infants born to mothers diagnosed with chorioamnionitis and infants born to mothers who did not have chorioamnionitis. The odds ratios (OR) to develop NEC in infants born to mothers affected by chorioamnionitis were calculated using chi square and Fisher Exact tests in the overall sample and in subgroups of different birthweight (BW) categories. The association was re-evaluated using logistic regression models to control for confounding variables. ResultsThe study identified 18,973,800 newborn infants admitted during the years 2016–2020. Among infants born to mothers with chorioamnionitis, NEC occurred in 0.9 % compared to 0.1 % in infants born to mothers without chorioamnionitis, (adjusted OR = 1.12, CI:1.02–1.15, p = 0.01). The prevalence of NEC in infants born to mothers with chorioamnionitis varied by the birth weight category, mainly for BW category 2500-4499 g (aOR = 1.61, CI:1.44–1.80, p < 0.001). ConclusionMaternal chorioamnionitis is associated with increased incidence of NEC, particularly in the BW category 2500-4499 g. Further studies are needed to examine the pathophysiological factors underlying this association.