AbstractTraditionally, disproportionality analysis (DPA) methods are employed for signal detection in pharmacovigilance, but these methods utilize only a limited portion of the data available from spontaneous event reports (SERs). This research aims to enhance signal detection by applying machine learning (ML) methods that can leverage additional data. We create a dataset by integrating SER data from the FDA Adverse Event Reporting System (FAERS) with biological and chemical data from DrugBank, and information on known adverse drug reactions (ADRs) from Side Effect Resource (SIDER). The known ADRs from SIDER are used to label the dataset for ML training. Using the AutoML library TPOT, ML models are trained on this dataset. Our findings indicate that ML models, even when trained with the same features as DPA methods, achieve higher recall and precision. Moreover, incorporating additional features related to drugs and events significantly boosts the performance of ML models. Analysis using the explainable AI (XAI) technique SHAP reveals that the drug name, event name, and fifth-level ATC code are the most influential features for model predictions. These ML models offer a promising alternative or supplement to conventional DPA methods for signal detection in pharmacovigilance.