OBJECTIVES: To identify and review the suitability of cystic fibrosis (CF)-specific clinical outcome assessments (COAs) for clinical trial assessment of novel CF therapies and to support product labelling.  METHODS: CF-specific COAs were identified through an in-depth literature search using pre-defined search terms and via clinicaltrials.gov. COA utilization in CF clinical trials and previous success in supporting product labelling was also explored. In line with best-practice, conceptual coverage of identified COAs was assessed by mapping items to a patient-centered conceptual model of CF symptoms and impacts. COAs with the most comprehensive conceptual coverage were further evaluated for content validity, psychometric properties and feasibility of use. RESULTS: Nine CF-specific COAs were identified; Cystic Fibrosis Questionnaire-Revised (CFQ-R) [pediatric 6-11/12-13 years, 14+ years and parent-report 6-13 years] and Cystic Fibrosis Respiratory Symptom Diary (CFRSD) were selected for in-depth review. CFQ-R 14+ provided the most comprehensive conceptual coverage, assessing 52% of patient-centered symptom concepts and 50% impact concepts. Pediatric and parent-reported versions of CFQ-R assessed fewer concepts. All versions of CFQ-R have acceptable psychometric properties and are linguistically validated in >30 languages. CFQ-R has also supported previous EMA and FDA label claims for respiratory symptoms. Limitations include the acceptability of a 2-week recall period and inconsistencies in concepts measured across pediatric and adult versions. CFRSD provides a comprehensive assessment of 83% of acute respiratory symptoms and 32% of acute impacts and is currently under evaluation for FDA Drug Development Tool qualification by FDA. The respiratory symptom score has excellent psychometric properties; impact items are yet to be validated. CONCLUSIONS: Although 9 CF-specific COAs were identified in this study, only the CFQ-R measures and CFRSD appear potentially suitable for assessment of CF-related symptoms and impacts in CF clinical trials. Further data relating to content validity of CFQ-R may be required to support future labelling approvals.