Background: Tuberculosis (TB) is an infectious disease caused by a bacterial infection. In Norway, screening immigrants for and treating latent TB infection (LTBI) is done to prevent active TB. LTBI, unlike active TB, does not cause symptoms but may cause progression (reactivation) to active TB later. The current screening strategy is a two-step strategy screening with tuberculin skin test (TST) and interferon gamma release assays (IGRA) when the TST is positive on immigrants from countries with a high prevalence of TB. A new screening strategy for LTBI where only IGRA is used will likely be introduced. Two other options, no LTBI-screening or screening only those with risk factors for reactivation may be considered as well because of potentially reduced costs. Before the new strategy is implemented the options for screening should be evaluated. Aim: The study was designed to compare the cost-effectiveness of four different screening strategies for LTBI in immigrants in Norway using cost-effectiveness analysis (CEA).The strategies were: (1) No screening for LTBI, (2) screening only people with risk factors for reactivation with IGRA, (3) screening all immigrants with TST and IGRA, and (4) screening all immigrants with IGRA only. Methods: A combined decision tree and Markov-model was developed where the outcome was avoided cases of active TB. The model was partially probabilistic. Costs were considered from a health budget perspective. Both deterministic and probabilistic sensitivity analyses (PSA) were conducted. Expected value of perfect information was estimated to indicate the potential gains from further research. Results: The results of the model indicate that the strategy combining TST and IGRA is not cost-effective at any willingness-to-pay (WTP) threshold. The three other screening-strategies were cost-effective at different thresholds of WTP. Screening all immigrants with IGRA was cost-effective at a WTP above NOK 222 000. Screening only immigrants with risk factors was cost-effective between a WTP of NOK 24 000 and NOK 222 000, while no LTBI-screening was cost-effective when WTP is below NOK 24 000. Conclusion: Going from the two-step model to IGRA would be cost-effective if the WTP is above NOK 222 000 per avoided case of active TB. No LTBI-screening or screening only immigrants with risk factors should be considered if the WTP is below NOK 222 000.