Although obesity has been hypothesized to worsen asthma, data from studies of subjects with well-characterized asthma are lacking.We sought to evaluate the relationship between body mass index (BMI), asthma impairment, and response to therapy.BMI (in kilograms per meter squared) and asthma phenotypic and treatment response data were extracted from Asthma Clinical Research Network studies. The cross-sectional relationship between BMI and asthma impairment was analyzed, as was the longitudinal relationship between BMI and response to asthma controller therapies.One thousand two hundred sixty-five subjects with mild-to-moderate persistent asthma were evaluated. Analyses of lean versus overweight/obese asthmatic subjects demonstrated small differences in FEV 1 (3.05 vs 2.91 L, P = .001), FEV 1 /forced vital capacity ratio (mean, 83.5% vs 82.4%; P = .01), rescue albuterol use (1.1 vs 1.2 puffs per day, P = .03), and asthma-related quality of life (5.77 vs 5.59, P = .0004). Overweight/obese asthmatic subjects demonstrated a smaller improvement in exhaled nitric oxide levels with inhaled corticosteroid (ICS) treatment than did lean asthmatic subjects (3.6 vs 6.5 ppb, P = .04). With ICS/long-acting β-agonist treatment, overweight/obese asthmatic subjects demonstrated smaller improvements in lung function than lean asthmatic subjects, with an 80 mL (P = .04) and 1.7% (P = .02) lesser improvement in FEV 1 and FEV 1 /forced vital capacity ratio, respectively. Significant differences in therapeutic response to leukotriene modifiers between BMI categories were not observed.Increased BMI is not associated with clinically significant worsening of impairment in subjects with mild-to-moderate persistent asthma. There is a modest association between increased BMI and reduced therapeutic effect of ICS-containing regimens in this patient population. Prospective studies evaluating the effect of being overweight or obese on treatment response in asthma are warranted.