Aims To assess the impact of RSV and other viral lower respiratory tract infections (LRTIs) on chronic respiratory morbidity in prematurely born infants and to investigate whether there were any functional or genetic predisposing factors. Methods One hundred and fifty three prematurely born infants were followed until one year corrected age with approximately half followed until two years of age. Lung function was measured at 36 weeks postmenstrual age (PMA) and one year corrected age. Blood or buccal swabs were taken for single nucleotide polymorphism (SNP) analysis. Following neonatal unit discharge, a nasopharyngeal aspirate (NPA) was taken whenever an infant had a LRTI. NPAs were analysed by real time PCR for 13 viruses. At one and two years corrected age healthcare utilisation and costs of care were calculated and parents completed a respiratory health related questionnaire and a diary card for one month. Results Infants developing RSV or other viral LRTIs requiring hospitalisation had reduced premorbid lung function compared to infants not hospitalised. Infants developing rhinovirus LRTIs had increased healthcare utilisation, cost of care and wheeze at one year corrected age. Infants developing RSV LRTIs had reduced lung function at one year corrected age. Prematurity was found to be a risk factor for developing RSV or other viral LRTIs but not influenza A (H1N1) LRTIs. A SNP in ADAM33 was associated with an increased risk of developing RSV LRTIs, but not with significant differences in 36 week PMA lung function results. SNPs in several genes were associated with increased chronic respiratory morbidity (IL10, NOS2A, SFTPC, MMP16 and VDR) and reduced lung function at one year (MMP16, NOS2A, SFTPC and VDR) in infants who had had RSV LRTIs. Conclusion In prematurely born infants, RSV and other viral LRTIs were associated with increased chronic respiratory morbidity at follow up, with some infants being genetically predisposed to this after RSV LRTI. Premorbid abnormal lung function predisposed to severe RSV and a SNP in the ADAM33 gene predisposed to RSV LRTIs.