BACKGROUND: Postoperative acute kidney injury (PO-AKI) prediction models for non-cardiac major surgeries typically rely solely on preoperative clinical characteristics. METHODS AND FINDINGS: In this study, we developed and externally validated a deep-learning-based model that integrates preoperative data with minute-scale intraoperative vital signs to predict PO-AKI. Using data from three hospitals, we constructed a convolutional neural network-based EfficientNet framework to analyze intraoperative data and created an ensemble model incorporating 103 baseline variables of demographics, medication use, comorbidities, and surgery-related characteristics. Model performance was compared with the conventional SPARK model from a previous study. Among 110,696 patients, 51,345 were included in the development cohort, and 59,351 in the external validation cohorts. The median age of the cohorts was 60, 61, and 66 years, respectively, with males comprising 54.9%, 50.8%, and 42.7% of each cohort. The intraoperative vital sign-based model demonstrated comparable predictive power (AUROC (Area Under the Receiver Operating Characteristic Curve): discovery cohort 0.707, validation cohort 0.637 and 0.607) to preoperative-only models (AUROC: discovery cohort 0.724, validation cohort 0.697 and 0.745). Adding 11 key clinical variables (e.g., age, sex, estimated glomerular filtration rate (eGFR), albuminuria, hyponatremia, hypoalbuminemia, anemia, diabetes, renin-angiotensin-aldosterone inhibitors, emergency surgery, and the estimated surgery time) improved the model's performance (AUROC: discovery cohort 0.765, validation cohort 0.716 and 0.761). The ensembled deep-learning model integrating both preoperative and intraoperative data achieved the highest predictive accuracy (AUROC: discovery cohort 0.795, validation cohort 0.762 and 0.786), outperforming the conventional SPARK model. The retrospective design in a single-nation cohort with non-inclusion of some potential AKI-associated variables is the main limitation of this study. CONCLUSIONS: This deep-learning-based PO-AKI risk prediction model provides a comprehensive approach to evaluating PO-AKI risk prediction by combining preoperative clinical data with real-time intraoperative vital sign information, offering enhanced predictive performance for better clinical decision-making.