BACKGROUND Chronic lung infection with Pseudomonas aeruginosa occurs in approximately 50% of patients with cystic fibrosis (CF). This infection further compromises lung function, and significantly contributes to the increased healthcare costs. OBJECTIVE Inhaled tobramycin, used to manage P. aeruginosa infection in CF patients, is available as powder (tobramycin inhalation powder, TIP) and solution (tobramycin inhalation solution, TIS). Evidence suggests increased adherence with the use of TIP over TIS. Hence, this analysis aimed to evaluate the potential pharmacoeconomic benefit of increased adherence with TIP over TIS in the US setting. METHODS A patient-level simulation model was developed to compare TIP with TIS. Both costs and benefits were predicted over a 10-year time horizon from a payer's perspective, and were discounted annually at 3%. All costs were presented in 2016 US dollars. RESULTS TIP was associated with greater quality-adjusted life-years (by 0.27) and lower total costs (by US$36,168) as compared with TIS over a 10-year time horizon. TIP-treated patients experienced a decreased mean number of exacerbations than TIS-treated patients (39.24 vs 50.20). Furthermore, administration of TIP via the T-326 Inhaler was associated with significant cost savings per patient, because of the nebulizer required for administering TIS (by US$1596) and exacerbation costs (by US$76,531). Probabilistic sensitivity analysis showed that TIP was dominant over TIS in 100% of the simulations. CONCLUSIONS TIP is likely to be a more cost-effective treatment than TIS, and therefore may reduce the economic burden of CF.