Trisomy 18 and trisomy 13 are associated with serious and/or fatal birth defects, with death frequently occurring in the first month of life. Previous studies are limited by small samples and are dated. This study characterized the comorbid birth defects associated with trisomy 18 and trisomy 13 among US liveborn infants using the Healthcare Cost and Utilization Project's Kids' Inpatient Database and Nationwide Inpatient Sample, two large, current and nationally representative databases. The occurrence of 39 commonly reported comorbid birth defects among infants with trisomies 18 and 13 was compared to the occurrence of malformations among newborns without trisomies. The prevalences of trisomy 18 and 13 were 1.29/10,000 and 0.85/10,000 live births, respectively. Among infants with trisomy 18, 61% were female, 45.4% with heart defects. Among those with trisomy 13, 53% were female, 38.4% had heart defects, 24.5% had orofacial anomalies, and 11.2% had central nervous system abnormalities. More than half of the newborns with both conditions died prior to discharge. This updated information can be used to inform clinical decision-making and may help providers better prepare families for infants with trisomies.