Background: Persistent eosinophilic airway inflammation in asthma increases the risk of exacerbations. In a phase 2b dose-ranging study, we aimed to assess the efficacy and safety of benralizumab, an anti-interleukin 5 receptor α monoclonal antibody that depletes blood and airway eosinophils, in adults with uncontrolled eosinophilic asthma. Methods: We did a randomised, controlled, double-blind, dose-ranging phase 2b study. Eligible participants were adults aged 18-75 years with uncontrolled asthma using medium-dose or high-dose inhaled corticosteroids and longacting β agonists, with two to six exacerbations in the past year. Current or former smokers were excluded. We used the ELEN index (an algorithm to predict elevated sputum eosinophils) or baseline fraction of exhaled nitric oxide to stratify patients by eosinophilic status, and with an interactive web-voice response system randomly assigned eosinophilic individuals in a 1:1:1:1 ratio to receive placebo, 2 mg benralizumab, 20 mg benralizumab, or 100 mg benralizumab, and non-eosinophilic individuals in a 1:1 ratio to receive placebo or 100 mg benralizumab. Study drugs were given as two subcutaneous injections every 4 weeks for the first three doses, then every 8 weeks, for 1 year. Patients, treating physicians, and study investigators were masked to treatment allocation. The primary endpoint was annual exacerbation rate in eosinophilic individuals after 1 year of follow-up. Analysis was by modified intention to treat. This study was designed with a two-sided α of 0·2 and powered at 78% for the primary outcome in the eosinophilic population. This study is registered with ClinicalTrials.gov, number NCT01238861. Findings: Between Jan 3, 2011, and March 6, 2012, we randomly assigned 324 eosinophilic individuals to placebo (n=80) or benralizumab 2 mg dose (n=81), 20 mg dose, (n=81), or 100 mg dose (n=82), and 285 non-eosinophilic individuals to 100 mg benralizumab (n=142, 140 included in analysis) or placebo (n=143, 142 included in analysis). In eosinophilic individuals, benralizumab reduced exacerbation rates compared with placebo in the 100 mg group (0·34 vs 0·57, reduction 41%, 80% CI 11 to 60, p=0·096) but not in the 2 mg group (0·65 vs 0·57, difference -9%, 80% CI -59 to 26, p=0·781) or the 20 mg group (0·37 vs 0·57, reduction 36%, 80% CI 3 to 58, p=0·173). In patients with a baseline blood eosinophil cutoff of at least 300 cells per μL, exacerbation rates in the benralizumab 20 mg group (n=70) and 100 mg group (n=97) were lower than in the placebo group (n=83; 0·30 vs 0·68, reduction 57%, 80% CI 33 to 72, p=0·015 for 20 mg dose; 0·38 vs 0·68, difference 43%, 80% CI 18 to 60, p=0·049 for 100 mg dose). Our findings suggested that benralizumab 20 mg and 100 mg resided at the dose-response plateau. Treatment-emergent adverse events occurred in 277 (72%) of 385 participants receiving any benralizumab dose compared with 143 (65%) of 221 receiving placebo. Nasopharyngitis (44 [11%] patients receiving benralizumab vs 13 [6%] patients receiving placebo) and injection site reactions (60 [16%] vs eight [4%]) occurred more frequently with benralizumab than with placebo. Interpretation: Benralizumab at 20 mg and 100 mg doses seemed to reduce asthma exacerbations in adults with uncontrolled eosinophilic asthma and baseline blood eosinophils of at least 300 cells per μL, possibly due to targeting of the interleukin 5 receptor rather than interleukin 5 ligand. Further investigation of benralizumab treatment in phase 3 studies is warranted. Funding: MedImmune.