We sought to describe contemporary outcomes and identify risk factors for hospital mortality in premature neonates with critical congenital heart disease who were referred for early intervention. Neonates who were born before 37 weeks’ gestation with critical congenital heart disease and admitted to our institution from 2002 to 2008 were included in this retrospective cohort study. Critical congenital heart disease was defined as a defect requiring surgical or transcatheter cardiac intervention or a defect resulting in death within the first 28 days of life. Logistic regression analyses were performed to identify risk factors for mortality before hospital discharge. The study included 180 premature neonates, of whom 37 (21%) died during their initial hospitalization, including 6 (4%) before cardiac intervention and 31 (17%) after cardiac intervention. For the 174 patients undergoing cardiac intervention, independent risk factors for mortality were a 5 min Apgar score ≤7, need for preintervention mechanical ventilation, and Risk Adjustment in Congenital Heart Surgery category ≥4 or not assignable. Mortality for premature infants with critical congenital heart disease who are referred for early intervention remains high. Patients with lower Apgar scores who receive preintervention mechanical ventilation and undergo more complex procedures are at greatest risk.