BACKGROUND AND AIMS: The risk of progression in Barrett's esophagus (BE) increases with development of dysplasia. There is a critical need to improve the diagnosis of BE dysplasia, given substantial interobserver disagreement among expert pathologists and overdiagnosis of dysplasia by community pathologists. We developed a deep learning model to predict dysplasia grade on whole-slide imaging. METHODS: We digitized nondysplastic BE (NDBE), low-grade dysplasia (LGD), and high-grade dysplasia (HGD) histology slides. Two expert pathologists confirmed all histology and digitally annotated areas of dysplasia. Training, validation, and test sets were created (by a random 70/20/10 split). We used an ensemble approach combining a "you only look once" model to identify regions of interest and histology class (NDBE, LGD, or HGD) followed by a ResNet101 model pretrained on ImageNet applied to the regions of interest. Diagnostic performance was determined for the whole slide. RESULTS: We included slides from 542 patients (164 NDBE, 226 LGD, and 152 HGD) yielding 8596 bounding boxes in the training set, 1946 bounding boxes in the validation set, and 840 boxes in the test set. When the ensemble model was used, sensitivity and specificity for LGD was 81.3% and 100%, respectively, and >90% for NDBE and HGD. The overall positive predictive value and sensitivity metric (calculated as F1 score) was .91 for NDBE, .90 for LGD, and 1.0 for HGD. CONCLUSIONS: We successfully trained and validated a deep learning model to accurately identify dysplasia on whole-slide images. This model can potentially help improve the histologic diagnosis of BE dysplasia and the appropriate application of endoscopic therapy.