Objectives: To verify whether early pulmonary mechanics measurements are useful to predict subsequent bronchopulmonary dysplasia (BPD) and its severity. Methods: Pulmonary mechanics were studied at 3, 5, 7 and 10 days of age in 52 preterm infants with birth weight < 1250 g, affected by respiratory distress syndrome and ventilated for more than 72 h. Pulmonary function was assessed using a previously standardized method based on the measurement of airflow with a Fleisch OO pneumotachograph and airway pressure with a model P7D differential pressure transducer. At 28 days pulmonary outcome was classified into three groups: no BPD, mild BPD (oxygen dependency and hazy lung on X-ray) and severe BPD (oxygen dependency and Northway stage 3/4). Results: Of the 52 infants, 39 survived to 28 days: no BPD (11 infants), mild BPD (16 infants) and severe BPD (12 infants). The no-BPD group had significantly higher gestational age and birth weight, fewer males and a lower incidence of patent ductus arteriosus than both BPD groups, while no differences were detected between the BPD groups. Lung compliance was significantly higher in the mild-BPD group than in the severe-BPD group at 7 and 10 days of life (p < 0.01 and p < 0.001, respectively). The corresponding odds ratio confirmed that ventilated infants with lower lung compliance values had a significantly higher probability of developing severe BPD. Respiratory system resistance did not show any predictive value. Conclusions: Our findings indicate that low lung compliance values determined on the 7th and 10th days of life are a reliable predictive tool of the severity of later BPD.