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In recent years, there has been a notable shift in the medical community's perspective regarding the use of diphenhydramine for allergic reactions, specifically for urticaria and anaphylaxis, stemming from its side effect profile and superior efficacy of second-generation antihistamines. Notably, the AAAAI's updated 2020 anaphylaxis guidelines recommended against use of first-generation antihistamines in the acute phase or to prevent biphasic reactions. Our study aimed to assess diphenhydramine utilization in US emergency departments (EDs) for anaphylaxis and urticaria from 2019 to 2021.