Background: Studies have documented inconsistent emergency anaphylaxis care and low compliance with published guidelines. Objective: To evaluate anaphylaxis management before and after implementation of an emergency department (ED) anaphylaxis order set and introduction of epinephrine autoinjectors, and to measure the effect on anaphylaxis guideline adherence. Methods: A cohort study was conducted from April 29, 2008, to August 9, 2012. Adult patients in the ED who were diagnosed with anaphylaxis were included. ED management, disposition, self-injectable epinephrine prescriptions, allergy follow-up, and incidence of biphasic reactions were evaluated. Results: The study included 202 patients. The median age of the patients was 45.3 years (interquartile range, 31.3-56.4 years); 139 (69%) were women. Patients who presented after order set implementation were more likely to be treated with epinephrine (51% vs 33%; odds ratio [OR] 2.05 [95% CI, 1.04-4.04]) and admitted to the ED observation unit (65% vs 44%; OR 2.38 [95% CI, 1.23-4.60]), and less likely to be dismissed home directly from ED (16% vs 29%, OR 0.47 [95% CI, 0.22-1.00]). Eleven patients (5%) had a biphasic reaction. Of these, 5 (46%) had the biphasic reaction in the ED observation unit; 1 patient was admitted to the intensive care unit. Six patients (55%) had reactions within 6 hours of initial symptom resolution, of whom 2 were admitted to the intensive care unit. Conclusions: Significantly higher proportions of patients with anaphylaxis received epinephrine and were admitted to the ED observation unit after introduction of epinephrine autoinjectors and order set implementation. Slightly more than half of the biphasic reactions occurred within the recommended observation time of 4 to 6 hours. Analysis of these data suggests that the multifaceted approach to changing anaphylaxis management described here improved guideline adherence. © 2014 American Academy of Allergy, Asthma & Immunology.