Adverse events were mostly mild (35%) or moderate (45%) in severity. One subject (0.9%) in the ivacaftor group had three adverse events considered life threatening: fatigue, depression, and suicidal ideation. Ten subjects (8.9%) in the ivacaftor group had 14 adverse events considered by the investigator to be severe; all were single events of nasal congestion, nasal polyps, epistaxis, increased viscosity of bronchial secretions, sinusitis, laryngitis, pulmonary exacerbation, diarrhea, dental caries, asthenia, rash, headache, arthritis, and nephrolithiasis. No severe events were reported in the placebo group. No deaths occurred during the study. Twenty-one subjects (15.0%) had at least one event that met the criteria for a serious adverse event, including 15 (13.4%) in the ivacaftor group and six (21.4%) in the placebo group. This difference was predominantly due to pulmonary exacerbations, which were more frequent in the placebo group (n = 5, 17.9%) than in the ivacaftor group (n = 10, 8.9%). Other serious adverse events were single events of hemoptysis, hypoxia, nasal polyps, abdominal pain, myopathy, fatigue, depression, and suicidal ideation in the ivacaftor group; and bronchopneumonia, cognitive disorder, and venous thrombosis in the placebo group.