Influenza is associated with adverse outcomes in children, although modification by additional medical conditions is not well-documented. We aimed to compare outcomes in children with versus without congenital heart defects (CHDs) who were hospitalized for influenza. We retrospectively evaluated patients 1-18y hospitalized for influenza in the Pediatric Health Information (PHIS) databasefrom 2004to2019. Outcomes were compared by CHD presence and then by CHD severity (minor biventricular, major biventricular, and single ventricle disease) using log-binomial regression adjusted for propensity scores accounting for ageat admission, sex, and history of asthma. Outcomes included inpatient mortality, intensive care unit (ICU) admission, mechanical ventilation, and length of stay (LOS) > 12days. To evaluate foreffect modification by genetic diagnoses, analyses were repeated stratified by CHD and genetic diagnosis. Among 55,161 children hospitalized for influenza, 2369 (4.3%) had CHDs, including 963 with minor biventricular, 938 with major biventricular, and 468 with single ventricle CHDs. Adjusting for propensity scores, children with CHDs had higher mortality (4.1% versus 0.9%) compared to those without CHDs (risk ratio [RR] 2.5, 95% confidence interval [CI] 1.9-3.4). Children with CHDs were at higher risk of mechanical ventilation (RR 1.6, 95% CI 1.6-1.7), ICU admission (RR 1.9, 95% CI 1.8-2.1), and LOS > 12days (RR 2.2, 95% CI 2.0-2.3). Compared to those with neither CHD nor genetic condition, children with both had significantly higher risk of all outcomes, with the largest difference for LOS > 12days (RR 2.3, 95% CI 2.0-2.7). Children with CHDs hospitalized for influenza are particularly susceptible to adverse outcomes compared to those without CHDs. Future studies are needed to corroborate findings in light of influenza vaccination.