© 2015 Elsevier Inc. Background Studies have demonstrated low rates of emergency department (ED) epinephrine administration for anaphylaxis patients, suggestive of ED undertreatment of anaphylaxis. Our study assessed the appropriateness of ED epinephrine administration in anaphylaxis management. Methods A prospective observational study was conducted involving ED patients presenting with possible allergic reactions. Patients and ED providers completed questionnaires regarding the suspected trigger, signs and symptoms, and prehospital treatment. Two board-certified allergists-immunologists independently reviewed the questionnaires, as well as electronic health records, to determine whether the cases represented anaphylaxis and whether ED epinephrine administration was appropriate. Results Among 174 patients enrolled in the study, 61 (35%) were confirmed to have anaphylaxis. Overall, 47 anaphylaxis patients (77%) received epinephrine either before ED arrival or in the ED. In the latter situation, 24 anaphylaxis patients (39%) received epinephrine and 37 (61%) did not. Of the patients who received ED epinephrine, the allergists-immunologists determined that its administration was appropriate in all cases (95% confidence interval [CI], 83%-100%). Among the 37 patients who did not receive ED epinephrine, the allergists-immunologists determined that nonadministration of epinephrine was appropriate in 36 patients (97%; 95% CI, 84%-100%). The allergists-immunologists determined that overall, ED management was appropriate for 60 (98%) of 61 patients with anaphylaxis (95% CI, 90%-100%). Conclusions Although more than 60% of anaphylaxis patients did not receive epinephrine in the ED, the allergists-immunologists deemed ED management appropriate in 98% of total cases. Previous retrospective studies may underestimate the appropriateness of ED anaphylaxis management, particularly when prehospital epinephrine administration is not reported.