Background Adrenal masses are common, but radiology reporting and recommendations for management can be variable. Purpose To create a machine learning algorithm to segment adrenal glands on contrast-enhanced CT images and classify glands as normal or mass-containing and to assess algorithm performance. Materials and Methods This retrospective study included two groups of contrast-enhanced abdominal CT examinations (development data set and secondary test set). Adrenal glands in the development data set were manually segmented by radiologists. Images in both the development data set and the secondary test set were manually classified as normal or mass-containing. Deep learning segmentation and classification models were trained on the development data set and evaluated on both data sets. Segmentation performance was evaluated with use of the Dice similarity coefficient (DSC), and classification performance with use of sensitivity and specificity. Results The development data set contained 274 CT examinations (251 patients; median age, 61 years; 133 women), and the secondary test set contained 991 CT examinations (991 patients; median age, 62 years; 578 women). The median model DSC on the development test set was 0.80 (IQR, 0.78-0.89) for normal glands and 0.84 (IQR, 0.79-0.90) for adrenal masses. On the development reader set, the median interreader DSC was 0.89 (IQR, 0.78-0.93) for normal glands and 0.89 (IQR, 0.85-0.97) for adrenal masses. Interreader DSC for radiologist manual segmentation did not differ from automated machine segmentation (P = .35). On the development test set, the model had a classification sensitivity of 83% (95% CI: 55, 95) and specificity of 89% (95% CI: 75, 96). On the secondary test set, the model had a classification sensitivity of 69% (95% CI: 58, 79) and specificity of 91% (95% CI: 90, 92). Conclusion A two-stage machine learning pipeline was able to segment the adrenal glands and differentiate normal adrenal glands from those containing masses. © RSNA, 2022 Online supplemental material is available for this article.