Abstract: The objective of this study was to identify patient and hospitalization characteristics associated with in-hospital mortality in infants with truncus arteriosus. We conducted a retrospective analysis of a large administrative database, the National Inpatient Sample dataset of the Healthcare Cost and Utilization Project for the years 2002-2017. We also sought to evaluate the resource utilization in the subgroup of subjects with truncus arteriosus and 22q11.2 deletion syndrome. Neonates with truncus arteriosus were identified by ICD-9 and ICD-10 codes. Hospital and patient factors associated with inpatient mortality were analyzed. Overall, 3009 neonates met inclusion criteria; a total of 326 patients died during the hospitalization (10.8%). Extracorporeal membrane oxygenation utilization was 7.1 %. Univariate and multivariate logistic regression analyses were used to identify risk factors for in-hospital mortality. Independent risk factors for mortality were prematurity (aOR = 2.43, 95% CI: 1.40–4.22, p = 0.002), diagnosis of stroke (aOR = 26.2, 95% CI: 10.1–68.1, p < 0.001), necrotizing enterocolitis (aOR= 3.10, 95% CI: 1.24-7.74, p=0.015) and presence of venous thrombosis (aOR = 13.5, 95% CI: 6.7–27.2, p < 0.001). Patients who received ECMO support or had cardiac catheterization procedure during the hospitalization had increased odds of mortality (aOR = 82.0, 95% CI: 44.5–151.4, p < 0.001, and aOR = 1.65, 95% CI: 0.98–2.77, p = 0.060, respectively). 22q11.2 deletion syndrome was associated with an inverse risk of death despite having more non-cardiac comorbidities; this patient subpopulation also had higher length of stay and increased cost of hospitalization.