To investigate the possibility that susceptibility to bronchopulmonary dysplasia (BPD) is affected by genetic factors, we analyzed risk factors for BPD in 108 twin pairs of infants having birth weight ≤1,500 g. When BPD occurred in a first born twin (n=23), it also occurred in 65% (n=15) of the second born twins, and when BPD did not occur in the first twin (n=85), it only occurred in 8% (n=7) of the second twins (crude odds ratio=20.9). After adjusting for potentially significant risk factors including birth weight, gestational age, gender, diagnosis of hyaline membrane disease, pneumothorax, symptomatic patent ductus arteriosus, and year of admission, using multiple logistic regression on the entire database (1,872 admissions ≤1,500 g), BPD status of a first twin remained a highly significant predictor of BPD in the second twin (adjusted odds ratio=12.3, P<.001). Other factors including birth order of twins, twin gestation, inborn/outborn status, cesarean section delivery, 1- and 5-minute Apgar scores, maternal race, maternal diabetes, and antepartum corticosteroid treatment were not significant predictors of BPD. These results are consistent with genetic factors affecting the susceptibility of very low birth weight premature infants to BPD, but we cannot exclude the possibility that factors not included in our analysis are also involved.