Objectives and study design: To evaluate the morbidity and mortality of preterm infants with congenital heart disease (CHD), a chart review was performed for infants with CHD, excluding isolated patent ductus arteriosus, who were <37 weeks’ gestation, weighed <2500 g, and were admitted to our neonatal intensive care unit from 1976 to 1999 (N = 201). Results: Patients in the study represented 1.9% of the total neonatal intensive care unit population <37 weeks’ gestation and <2500 g. The median gestational age was 33 weeks, and the mean birth weight was 1852 g. CHD diagnosis frequencies were similar to those reported in other large incidence studies, except for a higher percentage of conotruncal defects. The risk of necrotizing enterocolitis was 1.7 times higher and the overall mortality twice as high in our patients compared with patients in the neonatal intensive care unit who did not have CHD. Cardiac surgery (n = 133) was performed on 108 patients. During the recent period of 1985 to 1999, compared with our institution’s overall results for CHD surgery, the operative mortality rate was 10.4% versus 5.4% for closed procedures and 25.4% versus 10.5% for open procedures. The actuarial survival rate is 51% at 10 years; survival improved as the study period progressed. Conclusions: Infants with both CHD and prematurity did significantly worse than either group alone. Such outcome data are required for proper allocation of resources to care for this high-risk pediatric population. (J Pediatr 2000;137:653-9)