BACKGROUND: Severe uncontrolled asthma (SUA) is associated with increased asthma exacerbations. Whether high blood eosinophil counts are related to this burden is uncertain. OBJECTIVES: To determine the relationship of blood eosinophil counts to asthma exacerbations, utilization, and cost in patients with SUA. METHODS: Patients with persistent asthma (age >= 12 years) were identified administratively with SUA in phase I by evidencing (1) 2 or more asthma exacerbations; (2) 6 or more medium-or high-dose dispensed canisters of inhaled corticosteroid (ICS) as monotherapy or with long-acting beta(2)-agonist; and (3) 3 or more dispensed non-ICS controllers. Of the 541 patients with SUA invited to participate in the prospective phase II follow-up study, 261 (48.2%) had blood tests (index date) to determine eosinophil count and other atopic biomarkers. The relationship of blood eosinophil cutoff points to asthma exacerbations and direct costs 1 year after the index date were determined by multivariable regression. RESULTS: A blood eosinophil cutoff point of greater than or equal to 400 cells/mm(3) compared with less than 400 cells/mm(3), but not 150 cells/mm(3) or 300 cells/mm(3), was a risk factor in the outcome year in adjusted analyses for 2 or more asthma exacerbations (risk ratio, 1.55; 95% CI, 1.02-2.35; P = .04) and any asthma emergency department visit or hospitalization (risk ratio, 2.29; 95% CI, 1.16-4.55; P = .02), but not for rate of asthma exacerbations or incremental total direct asthma costs per patient ($ 202; 95% CI, -286 to 691). CONCLUSIONS: A high blood eosinophil count was an independent risk factor for 2 or more asthma exacerbations or any asthma emergency department visit or hospitalization, but not direct costs in patients with SUA, possibly constrained by limited power. (C) 2016 American Academy of Allergy, Asthma & Immunology