The objective of this analysis was to investigate whether patients with severe or difficult-to-treat asthma who experienced recent severe asthma exacerbations are at increased risk of future asthma exacerbations.We conducted a 1.5-year prospective analysis of 2780 patients 12 > or =years of age from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study. Severe exacerbations were defined as either an asthma-related emergency department visit or night of hospitalization in the 3 months prior to study visit; a secondary analysis assessed prior steroid bursts as an independent predictor and outcome. Potential confounding was assessed by statistical adjustment for demographic and clinical factors, as well as asthma severity and asthma control.Compared with patients without a recent severe exacerbation, patients with a recent exacerbation were at increased risk of future exacerbation (odds ratio=6.33; 95% CI 4.57, 8.76), even after adjustment for demographics and clinical factors (odds ratio=3.77; 95% CI 2.62, 5.43), asthma severity (physician-assessed: odds ratio=5.62; 95% CI 4.03, 7.83), National Asthma Education and Prevention Program (odds ratio=5.07; 95% CI 3.62, 7.11), Global Initiative for Asthma (odds ratio=5.32; 95% CI 3.80, 7.47), and asthma control (odds ratio=3.90; 95% CI 2.77, 5.50).This analysis suggests that recent severe asthma exacerbations are a strong independent factor predicting future exacerbations and, as such, should be considered as part of the clinical assessment of patients with severe or difficult-to-treat asthma.