Exercise is beneficial for patients with Cystic Fibrosis (CF) but long term effects of physical activity on lung function evolution are unknown. We evaluated the longitudinal relationship between changes in habitual physical activity (HPA) and rate of decline in lung function in patients with CF.We tracked HPA with the Habitual Activity Estimation Scale, FEV1 and Stage I exercise tests in 212 patients with CF over a nine year period.Adjusting for gender, baseline age and FEV1, mucoid Pseudomonas aeruginosa and CF related diabetes, FEV1 % predicted decreased by -1.63%/year (SD=0.08 p<0.0001) while HPA increased by 0.28 hours·day(-1)·year(-1) (SD=0.03 p<0.0001), over the study period. A greater increase in HPA was associated with a slower rate of decline in FEV1 (r=0.19, p<0.0069). Dividing into HIGH and LOW activity, (above or below the mean rate of change of activity respectively), a steeper rate of FEV1 decline was observed for LOW (-1.90%/year) compared to HIGH (-1.39%/year; p=0.002).Increases in HPA are feasible despite progression of lung disease and are associated with a slower rate of decline in FEV1, highlighting the benefit of regular physical activity, and its positive impact on lung function in patients with CF.