INTRODUCTION: Certain congenital cardiac lesions are at increased risk for the development of necrotizing enterocolitis (NEC). These patients with these lesions are often reliant on pulmonary and systemic vasomodulators to maintain adequate perfusion and oxygenation. This study sought to determine whether pulmonary or systemic vasodilator treatment is protective against the development of NEC in this population. METHODS: We used ICD codes to identify high-risk congenital cardiac disease patients ≤6 months of age, cared for at a tertiary children’s hospital between January 2011 and January 2021. Cardiac anomalies were stratified into ductal-dependent (pulmonary DD-P or systemic DD-S) or independent lesions. The rate of NEC development in those who received vasodilators (inhaled nitric oxide [iNO], pulmonary vasodilators, systemic vasodilators) was compared with controls in a multivariate analysis. RESULTS: Of the 353 patients who met inclusion criteria, 77.6% had ductal-dependent lesions (DD-S 41.9%, DD-P 35.7%), 19.5% received iNO, and 51.8% received other vasodilatory drugs. The overall NEC rate was 15.3%. On univariate analysis, DD-S, iNO use, and systemic vasodilators had a significantly higher risk of NEC, and DD-P was associated with lower NEC risk (Figure). On multivariate analysis, only iNO (odds ratio 2.725 [CI 1.36 to 5.44]) and DD-S (odds ratio 2.279 [CI 1.02 to 5.11]) were independent risk factors for NEC.FigureCONCLUSION: In patients with at-risk congenital cardiac disease lesions, a ductus-dependent systemic circulation and/or iNO treatment increases the risk of developing NEC. The presence of iNO or DD-S should be used as a marker of increased risk both in the prevention and workup of suspected NEC.