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The mortality rate for intensive care unit tuberculosis-destroyed lung (TDL) patients requiring mechanical ventilation (MV) remains high. We conducted a retrospective analysis of adult TDL patients requiring MV who were admitted to the intensive care unit of a tertiary infectious disease hospital in Chengdu, Sichuan Province, China from January 2019 to March 2023. Univariate and multivariate COX regression analyses were conducted to determine independent patient prognostic risk factors that were used to construct a predictive model of patient mortality. A total of 331 patients were included, the median age was 63.0 (50.0-71.0) years, 262 (79.2%) were males and the mortality rate was 48.64% (161/331). Training and validation data sets were obtained from 245 and 86 patients, respectively. Analysis of the training data set revealed that body mass index <18.5 kg/m2, blood urea nitrogen ≥7.14 mmol/L and septic shock were independent risk factors for increased mortality of TDL patients requiring MV. These variables were then used to construct a risk-based model for predicting patient mortality. Area under curve, sensitivity, and specificity values obtained using the model for the training data set were 0.808, 79.17%, and 68.80%, respectively, and corresponding values obtained using the validation data set were 0.876, 95.12%, and 62.22%, respectively. Concurrent correction curve and decision curve analyses confirmed the high predictive ability of the model, indicating its potential to facilitate early identification and classification-based clinical management of high-risk TDL patients requiring MV., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)