Allergy safety requires understanding the operational processes that expose patients to their known allergens, including how and when such processes fail. To improve health care safety for patients with allergies, we developed and assessed an allergy safety event classification schema to describe failures resulting in allergy-related safety events. Using keyword searches followed by expert manual review of 299,031 voluntarily-filed safety event reports at 2 large academic medical centers, we identified and classified allergy-related safety events from 5 years of safety reports. We used driver diagrams to elucidate root causes for commonly observed allergy safety events in health care settings. From 299,031 safety reports, 1922 (0.6%) were extracted with keywords and 744 (0.2%) were manually confirmed as allergy-related safety events. Safety failures were due to incomplete/inaccurate electronic health record documentation (n= 375, 50.4%), human factors (n= 175, 23.5%), allergy alert limitation and/or malfunction (n= 127, 17.1%), data exchange and interoperability failures (n= 92, 12.4%), and electronic health record system default options (n= 30, 4.0%). Safety failures resulted in known allergen exposures to drugs (n= 537), including heparin (n = 27) and topical anesthetics such as lidocaine (n = 8); latex (n= 114); food allergens (n= 73); and adhesive (n= 23). We identified 744 allergy-related safety events to inform a novel safety failure classification schema as an important step toward a safer health care environment for patients with allergies. Improved systems are required to address safety issues with certain food and drug allergens.