This study evaluated the use of high-resolution computed tomography (HRCT) to predict the presence of culture-positive pulmonary tuberculosis (PTB) in adult patients with pulmonary lesions in the emergency department (ED). The study included a derivation phase and validation phase with a total of 8,245 patients with pulmonary disease. There were 132 patients with culture-positive PTB in the derivation phase and 147 patients with culture-positive PTB in the validation phase. Imaging evaluation of pulmonary lesions included morphology and segmental distribution. The post-test probability ratios between both phases in three prevalence areas were analyzed. In the derivation phase, a multivariate analysis model identified cavitation, consolidation, and clusters/nodules in right or left upper lobe (except anterior segment) and consolidation of the superior segment of the right or left lower lobe as independent positive factors for culture-positive PTB, while consolidation of the right or left lower lobe (except superior segment) were independent negative factors. An ideal cutoff point based on the receiver operating characteristic (ROC) curve analysis was obtained at a score of 1. The sensitivity, specificity, positivity predictive value, and negative predictive value from derivation phase were 98.5% (130/132), 99.7% (3997/4008), 92.2% (130/141), and 99.9% (3997/3999). Based on the predicted positive likelihood ratio value of 328.33 in derivation phase, the post-test probability was observed to be 91.5% in the derivation phase, 92.5% in the validation phase, 94.5% in a high TB prevalence area, 91.0% in a moderate prevalence area, and 76.8% in moderate-to-low prevalence area. Our model using HRCT, which is feasible to perform in the ED, can promptly diagnose culture-positive PTB in moderate and moderate-to-low prevalence areas.