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Hospital-acquired pressure injuries (HAPIs) are a common and largely preventable complication in ICU patients, affecting 5–15% of cases and contributing to increased morbidity and healthcare costs. Despite standardized nursing protocols, incidence remains high, highlighting the need for more effective predictive and preventive approaches. While traditional tools like the Braden Scale offer interpretability, they lack sufficient predictive accuracy in critically ill populations. In contrast, machine learning models such as XGBoost and random forests improve prediction but function as black boxes, limiting clinical trust and actionable insight. To address this gap, this work proposes an Explainable Boosting Machine (EBM) framework trained on electronic health record (EHR) data from over 50,000 ICU admissions (2017–2023). EBMs combine strong predictive performance with interpretability by modeling feature effects through shape functions and capturing pairwise interactions. This allows identification of both global and patient-specific risk factors while maintaining transparency. The framework emphasizes modifiable factors such as repositioning frequency, nutrition, and medical device management, revealing nonlinear thresholds and interaction effects often missed by conventional methods. Overall, the proposed approach integrates accurate prediction with clear, clinically interpretable insights, enabling real-time identification of actionable risk factors for HAPI prevention. By bridging predictive modeling and nursing decision-making, it supports more targeted interventions and improved patient outcomes in critical care settings.