To conduct an economic evaluation of levofloxacin inhalation solution (LIS) compared to aztreonam lysine inhalation solution (AZLI) in Belgium for the treatment of chronic Pseudomonas aeruginosa lung infection in adult cystic fibrosis (CF) patients. A 24-week cycle Markov model was developed to estimate the expected costs and quality-adjusted life year (QALY) gains over three- and five-years. The model simulated the disease progression of CF patients as measured by the decrease in forced expiratory volume in 1 second (FEV1) percent predicted as well as lung transplantation and death. The base case analysis was conducted from the Belgian health care perspective at 3 years and sensitivity analysis at 5-years. In the base case LIS was dominant vs. AZLI over two studied time horizons from the health care perspective. LIS was associated with a gain in QALYs of 0.117 and 0.224 over three- and five-year time horizons, respectively, and was cost saving (-€515 and -€952, over three- and five-year time horizons, respectively) compared to AZLI. In addition to the base case analysis, two scenarios were conducted to assess the impact of parameter uncertainty on the model results. In all scenarios, conclusions are similar to the base case analysis: LIS was associated with a QALY gain and was cost-saving compared to AZLI. In general, the sensitivity analyses showed that the incremental cost-effectiveness ratio (ICER) was mainly sensitive to the costs of CF management and the mortality. The probability of ICER being less than €50,000 was 89.5%. This model simulated the disease progression of CF patients as measured by the decrease in FEV1 percent predicted. The base case results showed that the cost-effectiveness analysis of LIS is a dominant treatment option vs. AZLI over three- and five-year time horizons from the Belgian healthcare perspective.