Rationale There are limited longitudinal data about respiratory morbidity and lung function following preterm birth into adulthood. Objectives To determine the evolution of respiratory symptoms, spirometry and airway hyperresponsiveness of ex-preterm subjects from childhood into adulthood. Methods Ex-preterm subjects (median birthweight 1440g, median gestation 31.5 weeks) recruited at birth (not treated with surfactant), had excess respiratory symptoms, airways obstruction and increased airway hyperresponsiveness in mid-childhood. At a median age of 21.7 years, 60 of these subjects (the index study group) and 50 healthy term controls were recruited to determine respiratory morbidity and spirometry. Measurements Respiratory symptom questionnaire, spirometry and methacholine challenge test. Main Results The index study group had significantly more respiratory symptoms (16/60) than controls (4/50), odds ratio 4.2 (95% confidence interval [CI] 1.3 to 13.5, p=0.01), but no significant difference in measured spirometry. Specifically, in the index study group and controls, the mean z scores (95% CI of the group difference) for the first second forced expired volume (FEV₁) were -0.60 and -0.58 (-0.44 to 0.49) respectively (p=0.92); for the forced mid-expiratory flows (FEF_25-75) were -1.02 and -0.86 (-0.33 to 0.64) respectively (p=0.52), and for the forced vital capacity (FVC) were -0.29 and -0.33 (-0.46 to 0.38) respectively (p=0.85). Ex-preterm adults did not show evidence of increased airway hyper-responsiveness compared with controls, 23% and 19% respectively (p=0.89). Conclusions There are still excess respiratory symptoms 21 years following preterm birth. Reassuringly, this longitudinal study did not show evidence for persistent airways obstruction or airway hyper-responsiveness in ex-preterm adults.