Background: Screening of high-risk groups for TB is considered as the cornerstone for TB elimination but the measure of cost-effectiveness is also crucial in deciding the strategy for TB screening. This study aims to measure the cost-effectiveness of TB screening between the various high-risk groups in Malaysia.Methods: A decision tree model was developed to assess the cost-effectiveness of TB screening among the high-risk group from provider perspective using a secondary data from year 2016 to 2018. The outcome is presented in term of cost per TB case detected and the ICER. Deterministic and Probabilistic Sensitivity Analysis were also performed to measure the robustness of the model.Results: The most cost-effective strategy was TB screening among PL HIV, with MYR 2,597.00 per one TB case detected. This is followed by elderly, prisoners and smokers with MYR 2,868.62, MYR 3,065.24 and MYR 4,327.76 per one TB case detected respectively. There was an incremental costs of MYR 2.49 per screening, and 3.4 TB case detection per 1000 screening for TB screening among PL HIV in relation to TB screening among prisoners. The probability of symptomatic cases diagnosed as TB was the key driver for increasing cost effectiveness efficacy among PL HIV.Conclusions: Results of the study suggest prioritization of high-risk group TB screening programme by focusing on the most cost-effective strategy such as screening among PL HIV, prisoners and elderly, which has lower cost per TB case detected.