Background: Contacts of patients with multidrug-resistant tuberculosis (MDR -TB) are at risk of developing TB disease. Tuberculosis preventive treatment (TPT) is an intervention that can potentially reduce this risk. Objectives: To evaluate the effectiveness and safety of TPT for contacts of patients with MDR -TB. Data Sources: EMBASE, PubMed, Web of Science, and the Cochrane Library were searched for eligible studies on 24 July 2023, without start date restrictions. Study eligibility criteria: We included studies that compared TPT with no treatment in contacts of patients with MDR -TB and reported outcomes of progression to TB disease. Participants: Contacts of patients with MDR -TB. Interventions: TPT. Assessment of risk of bias: A modified version of the Newcastle -Ottawa Scale was used. Methods of data synthesis: Random -effects meta -analysis was utilized to calculate the relative risk for disease progression to TB in contacts of patients with MDR -TB who received TPT compared to those who did not. Additionally, completion, adverse effect, and discontinued rates were assessed. Results: Involving 1105 individuals from 11 studies, the pooled relative risk for disease progression in contacts receiving TPT versus those without treatment was 0.34 (95% CI: 0.16-0.72). Subgroup analysis indicated a lower pooled relative risk for regimens based on the drug -resistance profile of the index patients with TB compared to uniform treatment regimens (0.22 [95% CI: 0.06-0.84] vs. 0.49 [95% CI: 0.17-1.35]), although not statistically significant. The pooled completed rate was 83.8%, adverse effect rate was 22.9%, and discontinued rate was 6.5%. After excluding the levofloxacin and pyrazinamide regimen study, the completed rate increased to 88.0%, and adverse effects and discontinued rates decreased to 8.0% and 4.0%, respectively. Discussion: TPT reduces TB disease progression risk in contacts of patients with MDR -TB. Tailored TPT regimens based on drug -resistance profiles may offer additional benefits. Furthermore, efforts to improve completed rates and manage adverse effects are essential for optimizing effectiveness and safety. Guozhong Thou, Clin Microbiol Infect 2024;30:189 (c) 2023 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY -NC -ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).