Postpancreatectomy hemorrhage (PPH) is a rare yet dreaded complication following pancreaticoduodenectomy (PD). This retrospective study aimed to explore a machine learning (ML) model for predicting PPH in PD patients. A total of 284 patients who underwent open PD at our institute were included in the analysis. To address the issue of imbalanced data, the adaptive synthetic sampling (ADASYN) technique was employed. The best-performing ML model was selected using the PyCaret library in Python and evaluated based on recall, precision, and F1 score metrics. In addition to assessing the model's performance on the test data, bootstrap validation (n = 1000) with the original dataset was conducted. PPH occurred in 11 patients (3.9%), with a median onset time of 22days postoperatively. These minority cases were oversampled to 85 using ADASYN. The extra trees classifier demonstrated superior performance with recall, precision, and F1 score of 0.967, 0.914, and 0.937, respectively. Both validation using the test data and bootstrap resampling consistently demonstrated recall, precision, and F1 score exceeding 0.9. The model identified the peak value of C-reactive protein during the first 7 postoperative days as the most significant feature, followed by the preoperative neutrophil-to-lymphocyte ratio. This study highlights the potential of the ML approach to predict PPH occurrence following PD. Vigilance and early interventions guided by such model predictions could positively impact outcomes for high-risk patients.