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Background: Active screening for tuberculosis (TB) involves systematic detection of previously undiagnosed TB disease or latent TB infection (LTBI). It may be an important step toward elimination of TB among Inuit in Canada. We aimed to evaluate the cost-effectiveness of community-wide active screening for TB infection and disease in 2 Inuit communities in Nunavik. Methods: We incorporated screening data from the 2 communities into a decision analysis model. We predicted TB-related health outcomes over a 20-year time frame, beginning in 2019. We assessed the cost-effectiveness of active screening in the presence of varying outbreak frequency and intensity. We also considered scenarios involving variation in timing, impact and uptake of screening programs. Results: Given a single large outbreak in 2019, we estimated that 1 round of active screening reduced TB disease by 13% (95% uncertainty range -3% to 27%) and was cost saving compared with no screening, over 20 years. In the presence of simulated large outbreaks every 3 years thereafter, a single round of active screening was cost saving, as was biennial active screening. Compared with a single round, we also determined that biennial active screening reduced TB disease by 59% (95% uncertainty range 52% to 63%) and was estimated to cost Can$6430 (95% uncertainty range -$29131 to $13 658 in 2019 Can$) per additional active TB case prevented. With smaller outbreaks or improved rates of treatment initiation and completion for people with LTBI, we determined that biennial active screening remained reasonably cost-effective compared with no active screening. Interpretation: Active screening is a potentially cost-saving approach to reducing disease burden in Inuit communities that have frequent TB outbreaks., Tuberculosis (TB) was the world's deadliest infectious disease in 2019. (1) The burden of TB is disproportionately borne by vulnerable and marginalized communities, including Canadian Inuit, (2) where it reflects [...]