Background: A biphasic reaction is the recurrence of anaphylaxis symptoms within 72 hours of the initial anaphylactic event, without re-exposure to the trigger. Biphasic reactions are uncommon and unpredictable, and risk factors for biphasic reactions are poorly understood. Objective: To identify predictors of biphasic anaphylactic reactions in patients with anaphylaxis in the emergency department (ED). Methods: Patients of all ages who presented to the ED and met diagnostic criteria for anaphylaxis from April 2008 to January 2013 at an academic medical center with 73,000 annual patient visits were consecutively included. We collected data on patient characteristics, suspected triggers, signs and symptoms, ED management, and disposition. Univariate analyses were performed to estimate the association between potential predictor variables and biphasic reactions. We report associations as odds ratios (OR) and corresponding 95% CIs. Results: Among 541 patients with anaphylaxis, median age was 34.6 years (interquartile range, 18-52 years), and 320 (59%) were female patients. Twenty-one patients (4%) had biphasic reactions. Two pediatric patients, ages of 5 years old and 16 years old, developed a biphasic reaction. The median time between the resolution of initial symptoms and onset of the biphasic reaction was 7 hours (range, 1-72 hours). Biphasic reactions were associated with a history of prior anaphylaxis (OR 2.6 [95% CI, 1.1-6.4]; P = .029), unknown precipitant (OR 2.6 [95% CI, 1.1-6.2]; P = .03), symptoms of diarrhea (OR 4.5 [95% CI, 1.4-14.0]; P = .024), and wheezing (OR 2.6 [95% CI, 1.4-8.9]; P = .029). Conclusions: Patients with a history of prior anaphylaxis, an unknown precipitant, or who present with symptoms of diarrhea or wheezing may be at increased risk for a biphasic reaction. © 2014 American Academy of Allergy, Asthma & Immunology.