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To examine the possible association between increased nuchal translucency (NT) thickness in the first trimester and perinatal outcome in isolated congenital diaphragmatic hernia (CDH).We conducted a retrospective study between January 2004 and June 2010. The database was searched to identify all consecutive cases of CDH referred to the fetal medicine center of Necker Hospital in Paris. Enlarged NT was defined above the 95th centile. Only children born alive with an isolated CDH were selected for the analysis of prognostic factors. We also studied the correlation between NT thickness in the first trimester and lung-to-head ratio, observed to expected lung area-to-head ratio, lung volume estimated by magnetic resonance imaging, and other prenatal features of intrathoracic compression.Seventy-one cases of isolated CDH were available. The fetal NT was above the 95th centile in 9 of the 71 cases. Neonatal death occurred in 7/9 (78%) cases with enlarged NT, compared with 24/62 (38%) with normal NT (P = 0.035). Enlarged NT was significantly associated with prenatal features of intrathoracic compression.Enlarged NT thickness in CDH is associated with a poor outcome and is related to an early intrathoracic compression. © 2012 John Wiley & Sons, Ltd.