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Tuberculosis (TB) is the most common infectious disease in non-cystic fibrosis (CF) patients. Prolonged treatment is associated with undesirable side effects and a risk of developing antimicrobial resistance. An earlier study in Canada concluded that the use of five-drug antimicrobial prophylaxis for non-CF bronchiectasis (in combination with maintenance therapy) was cost-effective. This study was designed to assess the cost-effectiveness of extended antimicrobial prophylaxis for non-CF bronchiectasis in Canada. Monte Carlo probabilistic sensitivity analysis was used to estimate the effectiveness of different prophylactic regimens and the associated costs from a societal perspective. Model-based cost-effectiveness analysis was used to predict the incremental costs and incremental health outcomes associated with the different antimicrobial prophylaxis regimens. Model-based results were in good agreement with empirical findings. A five-drug regimen was associated with better health outcomes than a four-drug regimen. A six-drug regimen also had similar effectiveness to a five-drug regimen; however, this resulted in an increase in total