BackgroundAdopting a computational approach for the assessment of urine cytology specimens has the potential to improve the efficiency, accuracy, and reliability of bladder cancer screening, which has heretofore relied on semisubjective manual assessment methods. As rigorous, quantitative criteria and guidelines have been introduced for improving screening practices (e.g., The Paris System for Reporting Urinary Cytology), algorithms to emulate semiautonomous diagnostic decision‐making have lagged behind, in part because of the complex and nuanced nature of urine cytology reporting.MethodsIn this study, the authors report on the development and large‐scale validation of a deep‐learning tool, AutoParis‐X, which can facilitate rapid, semiautonomous examination of urine cytology specimens.ResultsThe results of this large‐scale, retrospective validation study indicate that AutoParis‐X can accurately determine urothelial cell atypia and aggregate a wide variety of cell‐related and cluster‐related information across a slide to yield an atypia burden score, which correlates closely with overall specimen atypia and is predictive of Paris system diagnostic categories. Importantly, this approach accounts for challenges associated with the assessment of overlapping cell cluster borders, which improve the ability to predict specimen atypia and accurately estimate the nuclear‐to‐cytoplasm ratio for cells in these clusters.ConclusionsThe authors developed a publicly available, open‐source, interactive web application that features a simple, easy‐to‐use display for examining urine cytology whole‐slide images and determining the level of atypia in specific cells, flagging the most abnormal cells for pathologist review. The accuracy of AutoParis‐X (and other semiautomated digital pathology systems) indicates that these technologies are approaching clinical readiness and necessitates full evaluation of these algorithms in head‐to‐head clinical trials.