Background <p>Acute kidney injury is associated with a prolonged hospital stay and high mortality for pediatric patients. The previous prediction models are based on a pre-defined time window which may affect its feasibility in clinical practice. This study aimed to develop and validate a real-time acute kidney injury risk prediction model for hospitalized pediatric patients.</p> Methods <p>Based on a retrospective cohort composed of eligible pediatric patients hospitalized in Beijing Children’s Hospital and Chongqing Children’s Hospital, a machine learning model to predict acute kidney injury occurrence was developed and validated. The prediction model was established using a stacking technique to combine three base learners including XGBoost, LightGBM, and CatBoost. Particle swarm optimization algorithm was used to tune hyperparameters. Next, we assessed the performance of the prediction model using the area under the receiver-operating curve and the area under the precision–recall curve.</p> Results <p>A total of 26,671 patients were included (20,967 in the derivation set, 5242 in the internal validation set, and 462 in the external validation set) contributing to 36,828 hospitalizations. The new proposed model had excellent performance for predicting any acute kidney injury within 24&#xa0;hours. Both the internal [area under the receiver-operating curve (AUROC) was 0.851, area under the precision–recall curve (AUPR) was 0.322] and external validation set (AUROC was 0.869, AUPR was 0.270) approved the model’s feasibility in predicting the risk of acute kidney injury.</p> Conclusion <p>The established risk predicting model can be used for real-time prevention of acute kidney injury in hospitalized pediatric patients.</p> Graphical abstract <p></p>