RATIONALE AND OBJECTIVES: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC). However, immune-related adverse events still occur, of which checkpoint inhibitor pneumonitis (CIP) is the most common. We aimed to construct and validate a contrast-enhanced computed tomography-based radiomic nomogram to predict the probability of CIP before ICIs treatment in NSCLC. MATERIALS AND METHODS: We retrospectively analyzed 685 patients with NSCLC who were initially treated with ICIs. A total of 186 patients were included in our study, and an additional 52 patients from another hospital were considered for external validation. After radiomics feature extraction and selection, we applied a support vector machine classification model to distinguish CIP and used the probability as a radiomics signature. A radiomics-clinical logistic regression model was built using the filtered clinical parameters and a radiomic signature. Receiver operating characteristic, area under the curve (AUC), calibration curve, and decision curve analysis was used for inter-model comparison. RESULTS: The combined radiomics-clinical model constructed using age, interstitial lung disease, emphysema at baseline, and radiomics signature showed an AUC of 0.935, 0.905, and 0.923 for the training, validation, and external validation cohorts, respectively. Compared with the clinical-only (AUC of 0.829, 0.826, and 0.809) and radiomics-only models (0.865, 0.847, and 0.841), the radiomics-clinical displayed better predictive power. CONCLUSION: This combined radiomics-clinical model predicted the probability of CIP during ICIs treatment in patients with NSCLC with favorable accuracy and could therefore be used as an effective tool to guide clinical ICIs decisions.