BACKGROUND Acute asthma is a common ED presentation. In a prospective, multicenter cohort study, we determined the frequency and factors associated with asthma relapse following discharge from the ED. METHODS Adults aged 18 to 55 years who were treated for acute asthma and discharged from 20 Canadian EDs underwent a structured ED interview and a follow-up telephone interview 4 weeks later. Standardized antiinflammatory treatment was offered at discharge. Multivariable analyses were performed. RESULTS Of 807 enrolled patients, 58% were women, and the median age was 30 years. Relapse occurred in 144 patients (18%) within 4 weeks of ED discharge. Factors independently associated with relapse occurrence were female sex (women, 22% vs men, 12%; adjusted OR aOR, 1.9; 95% CI, 1.2-3.0); symptom duration of ≥ 24 h prior to ED visit (long duration, 19% vs short duration, 13%; aOR, 1.7; 95% CI, 1.3-2.3); ever using oral corticosteroids (ever use, 21% vs never use, 12%; aOR, 1.5; 95% CI, 1.1-2.0); current use of an inhaled corticosteroid (ICS/long-acting β-agonist combination product (combination product, 25% vs ICS monotherapy,15%; aOR, 1.9; 95% CI, 1.1-3.2); and owning a spacer device (owning one, 24% vs not owning one, 15%; aOR, 1.6; 95% CI, 1.3-1.9). CONCLUSIONS Despite receiving guideline-concordant antiinflammatory treatments at ED discharge, almost one in five patients relapsed within 4 weeks. Female sex, prolonged symptoms, treatment-related factors, and markers of prior asthma severity were significantly associated with relapse. These results may help physicians target more aggressive interventions for patients at high risk of relapse.