Objective <p>This study aims to develop and validate an interpretable machine learning (ML) model for predicting post-procedural hemorrhage (PH) after ultrasound-guided percutaneous renal biopsy (PRB), aiding perioperative management.</p> Materials and methods <p>A retrospective analysis was conducted using data from 664 patients to develop and internally validate the predictive model. Key ultrasound parameters and clinical data were collected. The Boruta algorithm selected predictive factors. Eight ML models underwent hyperparameter tuning with 5-fold cross-validation, using the area under the curve (AUC) to determine the best model, which was further validated externally (<i>n</i> = 137). Model interpretation was enhanced using SHAP values.</p> Results <p>Important predictive factors identified included renal parenchymal thickness (RPT), distance from the puncture point to the lower edge of the kidney (D1), and the ratio of D1 to the Renal length (R1), disease course, eGFR and prothrombin time (PT). The random forest model outperformed others with AUCs of 0.831, 0.784, and 0.776 for the training, internal validation, and external validation sets, respectively, displaying an accuracy of 0.742, sensitivity of 0.675, specificity of 0.805, and F1 score of 0.691. SHAP analysis highlighted prolonged PT, thinner RPT, smaller D1, lower eGFR, and extended disease course as increasing PH risk.</p> Conclusion <p>The random forest model effectively predicts PH post-PRB, supporting early diagnosis and decision-making.</p>