Histopathological assessment of esophageal biopsies is a key part in the management of patients with Barrett esophagus (BE) but prone to observer variability and reliable diagnostic methods are needed. Artificial intelligence (AI) is emerging as a powerful tool for aided diagnosis but often relies on abstract test and validation sets while real-world behavior is unknown. In this study, we developed a 2-stage AI system for histopathological assessment of BE-related dysplasia using deep learning to enhance the efficiency and accuracy of the pathology workflow. The AI system was developed and trained on 290 whole-slide images (WSIs) that were annotated at glandular and tissue levels. The system was designed to identify individual glands, grade dysplasia, and assign a WSI-level diagnosis. The proposed method was evaluated by comparing the performance of our AI system with that of a large international and heterogeneous group of 55 gastrointestinal pathologists assessing 55 digitized biopsies spanning the complete spectrum of BE-related dysplasia. The AI system correctly graded 76.4% of the WSIs, surpassing the performance of 53 out of the 55 participating pathologists. Furthermore, the receiver-operating characteristic analysis showed that the system's ability to predict the absence (nondysplastic BE) versus the presence of any dysplasia was with an area under the curve of 0.94 and a sensitivity of 0.92 at a specificity of 0.94. These findings demonstrate that this AI system has the potential to assist pathologists in assessment of BE-related dysplasia. The system's outputs could provide a reliable and consistent secondary diagnosis in challenging cases or be used for triaging low-risk nondysplastic biopsies, thereby reducing the workload of pathologists and increasing throughput.