OBJECTIVES: Ivacaftor is a breakthrough treatment for cystic fibrosis (CF) patients with the G551D genetic mutation. Clinical trials show ivacaftor significantly improves lung function. Information on lifetime clinical effects and cost are lacking. This study aims to forecast lifetime outcomes and cost by comparing ivacaftor plus usual care versus usual care alone. METHODS: A lifetime Markov model of ivacaftor for G551D mutation CF patients aged ≥6 years was conducted from a United States payer perspective. The model consisted of 5 health states: 1) forced expiratory volume 1-second (FEV) % predicted >70%, 2) 40%≤FEV≤70%, 3) FEV<40%, 4) Lung transplantation, and 5) Death. All inputs were determined by literature sources.  Efficacy of ivacaftor was from previous randomized clinical trials for the first 2 years. The efficacy after 2 years was assumed half of the observed efficacy (consistent with United Kingdom assessment assumption). The budget impact was estimated.  We indirectly estimated ivacaftor’s improvement in CF outcome gaps compared to the non-CF population. RESULTS: Compared to the usual care alone, ivacaftor treatment was associated with 18.09 additional life-years [(95% credible interval (CI); 14.63-21.13] and 14.92 additional quality-adjusted life-years (QALYs) [95%CI; 11.92 – 17.95] over an average lifetime. Moving from usual care alone to ivacaftor treatment was associated with reducing the survival and QALY gaps of the non-CF population by 52.32% and 44.29%, respectively. The incremental lifetime cost with 3% discount was $3,740,480. The budget impact was $0.09 per-member per-month [95% CI; $0.07 to $0.11].  CONCLUSIONS: Ivacaftor was forecasted to increase life-years and QALYs in CF patients with the G551D mutation and move morbidity and mortality outcomes closer to that of their non-CF peers. The overall cost in patients with ivacaftor is much higher than usual care, but comes at a relatively low budget impact.  Uncertainty in this literature-informed analysis could be reduced with patient-level analyses.