Background: To date, radiographic sign clusters of multidrug-resistant pulmonary tuberculosis (MDR-TB) patients have not been reported. We conducted a study to investigate the classification and prognosis of sign clusters in pulmonary Computed Tomography (CT) images from patients with MDR-TB for the first time by using principal component analysis (PCA).Methods: The clinical data and pulmonary CT findings of 108 patients with MDR-TB in the Liupanshui Third Hospital were collected (from January 2018 to December 2020). PCA was used to analyze the sign clusters on pulmonary CT, and receiver operating characteristic (ROC) analysis was used to analyze the predictive value of the treatment outcome of MDR-TB patients.Results: Six cluster signs of MDR-TB were determined by PCA: nodules, infiltration, consolidation, cavities, destroyed lung and non-active lesions. Nine months after treatment, the area under the ROC curve (AUC) of MDR-TB patients with a cavity sign cluster was 0.818 (95% CI: 0.733–0.886), and the positive predictive value (PPV) and negative predictive value (NPV) of the treatment outcome were 79.6% (95% CI: 65.7–89.8%) and 72.9% (95% CI: 59.7–83.6%), respectively.Conclusion: PCA plays an important role in the classification of sign groups on pulmonary CT images of MDR-TB patients, and the sign clusters obtained from PCA are of great significance in predicting the treatment outcome.