The aim of our study is to compare the three-dimensional (3D) ultrasound fetal lung volume measurements with two-dimensional (2D) ultrasound biometric parameters in predicting pulmonary hypoplasia (PH). From June 2006 to November 2008, we identified 35 fetuses at high risk for developing PH, including premature preterm rupture of membranes (17), fetal skeletal malformations (7), hydrothorax (7), and bilateral renal dysplasia (4). 3D lung volumes adjusted for gestational age (GA) or estimated fetal weight (EFW), thoracic circumference adjusted for GA or femur length, thoracic/abdominal circumference ratio, and thoracic/heart area ratio were measured. Three infants were excluded because no clinical or histological information regarding lung hypoplasia was available. Of the 32 remaining infants, 13 (41%) were diagnosed with PH at postmortem examination or by clinical and radiological examination. 3D lung volume measurements had a better diagnostic accuracy for predicting PH either when adjusted for GA [sensitivity, 12/13 (92%); specificity, 16/19 (84%); positive predictive value 12/15 (80%); negative predictive value, 16/17(94%)] or EFW [sensitivity, 11/13 (85%); specificity, 18/19 (94%); positive predictive value 11/12(92%); negative predictive value, 18/20(90%)] compared to the 2D biometric measurement. 3D lung volume measurements seem to be useful in the prenatal prediction of PH.