Accurate prediction of Adverse Drug Reactions (ADRs) at the patient level is essential for ensuring patient safety and optimizing healthcare outcomes. Traditional machine learning‐based methods primarily focus on predicting potential ADRs for drugs, but they often fall short of capturing the complexity of individual demographics and the variations in ADRs experienced by different people. In this study, a novel framework called Precise Adverse Drug Reaction (PreciseADR) for patient‐level ADR prediction is proposed. The approach effectively integrates relations between patients and ADRs, and harnesses the power of heterogeneous Graph Neural Networks (GNNs) to address the limitations of traditional methods. Specifically, a heterogeneous graph representation of patients is constructed, encompassing nodes that represent patients, diseases, drugs, and ADRs. By leveraging edges in the graph, crucial connections are captured such as a patient being affected by diseases, taking specific drugs, and experiencing ADRs. Next, a GNN‐based model is utilized to learn latent representations of the patient nodes and facilitate the propagation of information throughout the graph structure. By employing patient embeddings that consider their diseases and drugs, potential ADRs can be accurately predicted. The PreciseADR is dedicated to effectively capturing both local and global dependencies within the heterogeneous graph, allowing for the identification of subtle patterns and interactions that play a significant role in ADRs. To evaluate the performance of the approach, extensive experiments are conducted on a large‐scale real‐world healthcare dataset with adverse reports from the FDA Adverse Event Reporting System (FAERS). Experimental results demonstrate that the PreciseADR achieves superior predictive performance in identifying patient‐level ADRs, surpassing the strongest baseline by 3.2% in AUC score and by 4.9% in Hit@10.
