BACKGROUND: Postnatal assessment of disease severity is critical for analysis of mortality rates and development of future interventions in congenital diaphragmatic hernia (CDH). OBJECTIVE: The objective of this study was to stratify the risk of mortality based on arterial Paco 2. METHODS: Retrospective analysis of infants (n = 133) with CDH admitted to a regional extracorporeal membrane oxygenation (ECMO) center in two different periods: period I (1987-1996; n = 46) and period II (2002-2010; n = 87). RESULTS: The mortality rate (37%) was similar in both periods (p = 0.98). Paco 2 < 60 mm Hg in the first arterial blood gas (ABG) was an independent predictor of survival in both periods (p = 0.03). The predicted survival rate was 84% if initial Paco 2 was < 55 mm Hg. For infants with initial Paco 2 > 55 mm Hg treated with ECMO (n = 83), the predicted survival rate was 11% if the Paco 2 was > 88 mm Hg before the initiation of ECMO. CONCLUSION: Paco 2, a surrogate of lung hypoplasia, may be useful for risk stratification in CDH. Paco 2 < 60 mm Hg in the first ABG may indicate milder pulmonary hypoplasia. A Paco 2 > 80 mm Hg in the first ABG and/or before ECMO may indicate severe pulmonary hypoplasia.