It is unknown why respiratory syncytial virus (RSV) causes mild disease in some children and severe disease, requiring hospitalisation, in others. We aimed to assess whether diminished premorbid lung function in healthy term infants predisposes to hospitalisation during RSV bronchiolitis, and to post-RSV wheeze. In a prospective birth cohort study of unselected term healthy children, neonatal lung function was measured before the age of 2 months (n=2133). From birth through the first year of life, respiratory symptoms were recorded in a diary, and general practitioner consultations and hospitalisations were documented. In a subgroup (n=417) repeated nose and throat swabs were collected for PCR to detect RSV infections. Median neonatal respiratory system compliance (Crs) was significantly lower (41.2 versus 47.4 mL · kPa(-1), p=0.03) and resistance (Rrs) was higher (8.2 versus 6.3 kPa · s · L(-1), p=0.10) in hospitalised RSV patients (n=18) compared with nonhospitalised RSV-positive infants (n=84). Every 10 mL · kPa(-1) increase in Crs was associated with 55% less post-RSV wheeze (OR 0.56, 95% CI 0.35-0.90), and each kPa · s · L(-1) increase in Rrs was associated with 42% more post-RSV wheeze, which was only marginally explained by pre-RSV wheeze or severity of the RSV disease. This unselected birth cohort study shows for the first time that decreased lung function at birth predisposes to severe RSV disease, and to post-RSV wheeze.