OBJECTIVES: This review aims to appraise the clinical and cost effectiveness of ivacaftor for oral administration for the treatment of cystic fibrosis (CF) in patients age six years and elder who have at least one G551D mutation in the CFTR (cystic fibrosis transmembrane conductance regulator) gene.  METHODS: A limited literature search was conducted of key resources, and titles and abstracts of the retrieved publications were reviewed. Full-text publications were evaluated for final article selection according to predetermined criteria (population, intervention, comparator, outcomes, and study designs). RESULTS: A review of the clinical efficacy of ivacaftor, its comparative clinical efficacy compared with dornase alfa, and a review of the cost-effectiveness of ivacaftor will help to inform decisions about the treatment of patients with CF. Four studies were presented as evidence of the benefit of ivacaftor in CF. Two pivotal trials STRIVE and ENVISION, one open label extension study, PERSIST, for patients in STRIVE and ENVISION and a final study in different patient group, DISCOVER, in patients who are homozygous for the F508del mutation. The percent predicted forced expiratory volume in 1 second (FEV1) was the primary outcome measure for the two phase III clinical trials. The review group noted the absence of long term efficacy data particularly in relation to the benefit of ivacaftor in maintaining percent predicted FEV1 and reducing pulmonary exacerbations and the resultant impact on survival rates. The analysis for this extrapolation is based on a number of prediction models that have been published. The disease progression model predicts that the median survival for a patient treated with ivacaftor will be 29.2 years longer as a consequence of taking the drug. CONCLUSIONS: Whilst ivacaftor may represent an innovation for the treatment of patients with cystic fibrosis there are significant uncertainties, including the absence of long term health outcome data.