Background and objectiveCardiovascular disease (CD) is a major global health concern, affecting millions with symptoms like fatigue and chest discomfort. Timely identification is crucial due to its significant contribution to global mortality. In healthcare, artificial intelligence (AI) holds promise for advancing disease risk assessment and treatment outcome prediction. However, machine learning (ML) evolution raises concerns about data privacy and biases, especially in sensitive healthcare applications. The objective is to develop and implement a responsible AI model for CD prediction that prioritize patient privacy, security, ensuring transparency, explainability, fairness, and ethical adherence in healthcare applications. MethodsTo predict CD while prioritizing patient privacy, our study employed data anonymization involved adding Laplace noise to sensitive features like age and gender. The anonymized dataset underwent analysis using a differential privacy (DP) framework to preserve data privacy. DP ensured confidentiality while extracting insights. Compared with Logistic Regression (LR), Gaussian Naïve Bayes (GNB), and Random Forest (RF), the methodology integrated feature selection, statistical analysis, and SHapley Additive exPlanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME) for interpretability. This approach facilitates transparent and interpretable AI decision-making, aligning with responsible AI development principles. Overall, it combines privacy preservation, interpretability, and ethical considerations for accurate CD predictions. ResultsOur investigations from the DP framework with LR were promising, with an area under curve (AUC) of 0.848 ± 0.03, an accuracy of 0.797 ± 0.02, precision at 0.789 ± 0.02, recall at 0.797 ± 0.02, and an F1 score of 0.787 ± 0.02, with a comparable performance with the non-privacy framework. The SHAP and LIME based results support clinical findings, show a commitment to transparent and interpretable AI decision-making, and aligns with the principles of responsible AI development. ConclusionsOur study endorses a novel approach in predicting CD, amalgamating data anonymization, privacy-preserving methods, interpretability tools SHAP, LIME, and ethical considerations. This responsible AI framework ensures accurate predictions, privacy preservation, and user trust, underscoring the significance of comprehensive and transparent ML models in healthcare. Therefore, this research empowers the ability to forecast CD, providing a vital lifeline to millions of CD patients globally and potentially preventing numerous fatalities.