Purpose: During the 24-week inhaled steroid dose-stable phase of a double-blind, randomized, controlled trial in children ≥6 to < 12 years old with inadequately controlled, moderate-to-severe, allergic asthma, clinically significant asthma exacerbation rates were reduced by 31% (p=0.007) with omalizumab (75-375 mg every 2 or 4 weeks) versus placebo. We previously showed that baseline blood eosinophil count is a predictive biomarker for omalizumab response in these children and have further extended these analyses to examine other indicators of asthma severity and omalizumab response. Methods: In this post hoc exploratory Poisson regression analysis, we examined reductions in asthma exacerbation rates with omalizumab versus placebo during the 24-week inhaled steroid dose-stable phase of a double-blind, randomized, controlled trial in children ≥6 to < 12 years old with inadequately controlled, moderate-to-severe, allergic asthma. Children were stratified into subgroups by baseline percentage-predicted forced expiratory volume in 1 s (ppFEV1) above or below 90% and by < 3 or ≥3 clinically significant exacerbations during the previous year. Clinically significant exacerbations were defined as those requiring either systemic corticosteroid therapy or a double dose of baseline inhaled corticosteroid for ≥3 days. Results: Baseline demographic characteristics were similar between treatment groups and within strata, except mean weight, which was slightly higher in the subgroups with ppFEV1 < 90% and ≥3 exacerbations during the previous year. Subgroups had mean (SD) baseline ages between 8.1 (1.7) and 8.9 (1.7) years. Reduction in exacerbation rates (95% CI) with omalizumab versus placebo (Figure) were: Baseline ppFEV1 < 90%, −36% (−53, −13; p=0.004); ≥90%, −22% (−52, 27; p=0.32) and < 3 exacerbations in the previous year, −20% (−45, 16; p=0.24); ≥3, −42% (−60, −14; p=0.006). Conclusion: Although these hypothesis-generating analyses were not powered for subgroup analyses, a significantly greater response to omalizumab was observed for asthma exacerbation reduction compared with placebo among the subgroups of children with baseline ppFEV1 < 90% or a history of ≥3 protocol-defined exacerbations during the previous year. Reductions in exacerbation rates were also observed with omalizumab versus placebo among subgroups of children with baseline ppFEV1 ≥90% or < 3 protocol-defined exacerbations during the previous year, but were not statistically significant. Further prospective studies are needed to validate these findings.