Cystic fibrosis (CF) is due to a mutation in the CF conductance transmembrane regulator (CFTR) gene, which codes for the CFTR protein. CFTR regulates chloride transport in multiple organs, including the lungs. To date, more than 1,800 mutations have been identified, which can be divided into six classes. Class III (gating) mutations result in a chloride channel that is correctly localized at the cell surface but fails to open and close correctly. Ivacaftor increases channel open probability (gating) of class III mutations and, in clinical trials, produced significant increases in FEV1 (> 10% absolute) and weight as well as reductions in sweat chloride level and pulmonary exacerbations in patients aged ≥ 6 years with one of nine gating mutations.1,2 It is licensed for treating patients with CF with nine gating mutations (G551D, G551S, G1349D, G1244E, G970R, G178R, S549N, S549R, S1251N, and S1255P) and in December 2014 was approved by the US Food and Drug Administration for patients with the R117H mutation.3 The R117H mutation is a class IV (conductance) mutation in which CFTR is correctly localized at the cell surface but conducts chloride abnormally. Preliminary trial data suggest ivacaftor produces a 5% absolute increase in FEV1 in patients aged ≥ 18 years who carry the R117H mutation.4,5 However, this study excluded patients with severe disease (FEV1 < 40% predicted). Although data demonstrate the usefulness of ivacaftor in patients with severe CF who have gating mutation,6-8 its use in severe CF with class IV mutations has thus far not been described.