Abstract As the 6th leading chronic disease in the U.S., allergies affect 30% of adults and 40% of children. Adverse drug reactions occur in 1 in 4 outpatients and 1 in 5 inpatients. Many allergies and adverse reactions warrant documentation in the electronic health record (EHR) allergy section to inform future medical care and prescribing. It is critical to obtain a complete and accurate allergy history for each patient and to provide clinicians with an efficient allergy-alerting clinical decision support (CDS) tool. However, the allergy modules in most existing EHRs have serious limitations in how allergies are documented and drug allergy alerts are fired. These include: frequently missing documentation of reaction mechanism and type, lack of a comprehensive terminology subset for encoding diverse reactions, insufficient tools for reconciling allergy information, and physician alert fatigue resulting from an alert override rate of greater than 90%. In this study, we will provide solutions to these challenges by addressing the following specific aims: 1) improve reaction documentation by developing a comprehensive and interactive value set; 2) develop an innovative allergy reconciliation module within the EHR; 3) redesign drug allergy alerting mechanisms; and 4) distribute our methods and tools to healthcare institutions and the research community.