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Objective: To evaluate the potential of three-dimensional ultrasound to predict outcome in congenital diaphragmatic hernia., Design: Prospective observational study., Setting: Tertiary care centre., Population: Twelve cases of isolated congenital diaphragmatic hernia (11 left-sided, 1 right-sided) and 109 controls., Methods: Fetal lung volume was assessed by three-dimensional ultrasound using the technique of rotation of the multiplanar imaging. In the control fetuses, a logistic transformation was performed to correlate fetal lung volume with gestational age, and the confidence interval was obtained with a bootstrap resampling. A mathematical equation was then obtained allowing calculation of the expected fetal lung volume as a function of gestational age. In fetuses with congenital diaphragmatic hernia, the observed/expected lung volume ratio was compared with postnatal outcome., Main Outcome Measures: Neonatal mortality and pulmonary hypoplasia, which was defined as lung/body weight ratios less than 0.012., Results: The expected fetal lung volume was derived from the mathematical equation: Fetal lung volume (mL) = exp (4.72/(1 + exp ((20.32 - gestational age in weeks)/6.05))). The observed/expected fetal lung volume ratio was significantly lower in the congenital diaphragmatic hernia group (median: 0.34, range: 0.16-0.66), than in the control group (median: 1.02, range: 0.62-1.97, P < 0.0001). The distribution of this ratio was significantly downshifted in the infants with congenital diaphragmatic hernia who died (median: 0.19, range: 0.18-0.66) compared with survivors (median: 0.44, range: 0.36-0.66, P= 0.04). The observed/expected fetal lung volume ratio was also correlated with the postmortem lung/body weight ratio., Conclusion: In isolated congenital diaphragmatic hernia, fetal lung volume measurement by three-dimensional ultrasound is a potential predictor for pulmonary hypoplasia and postnatal outcome.