The emergence of new treatments in Cystic Fibrosis (CF) has emphasised the need for sensitive, repeatable, responsive and feasible measures of lung disease. FEV I is limited as an assessment tool as it is insensitive to changes in the peripheral airways. Lung Clearance Index (LCI) is proposed as an outcome measure for the detection of early lung disease and use in CF clinical trials. The use of LCI in CF is supported by the large number of studies demonstrating its robustness. However, most studies have been performed in children, with only approximately 20% of studies including adults. The aim of this study was to examine the clinimetric properties of LCI and to assess the relationships between LCI and other physiological, clinical and microbiological markers of disease in a CF child and adult group. Results of this study show that LCI had good intra and inter-visit repeatability over a longer term period. LCI had superior sensitivity to lung function abnormality and Pseudomonas aeruginosa infection, compared to FEV 1 % predicted. On assessment of routine microbiological culture results, subjects with P. aeruginosa alone had the worst LCI. Extended culture methods to detect the entire airway micro biota composition, showed that subjects with a smaller load of anaerobic bacteria had a worse LCI. LCI also correlated with biomarkers of inflammation. These results suggest that LCI may be sensitive to differences in airway microbial community composition and inflammation. Compared to spirometry, LCI correlated with more patient reported symptom and health related quality of life questionnaire scores. However, the response of LCI with intravenous antibiotic treatment for pulmonary exacerbation was not statistically significant. FEV I % predicted may be more responsive across the disease severity range in this setting. Overall, this study has shown that LCI is a robust, sensitive and meaningful measure for use in clinical trials during clinical stability, across the age range in CF.