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Current evidence regarding the relationship between childhood obesity, decreased response to inhaled corticosteroids (ICSs), and poor asthma control is conflicting.We assessed whether obesity (1) is associated with time to first exacerbation among children with asthma initiating step 3 maintenance therapies and (2) modifies the effectiveness of step 3 therapies.A retrospective cohort study was conducted from clinical data linked to health and drug administrative databases. The cohort consisted of children aged 2 to 18 years with specialist-confirmed asthma who initiated medium/high-dose ICS monotherapy or low/medium-dose ICS with leukotriene receptor antagonist/long-acting β-agonist (combination therapy) at the Montreal Children's Hospital Asthma Center from 2000 to 2007. Children were classified as exposed to step 3 therapies when they were dispensed a corresponding drug claim during follow-up, whereas those without claims were classified as nonadherers. Marginal structural Cox models were used to estimate the effect of obesity (body mass index > 97th percentile) and treatment on time to exacerbation, which was defined as any emergency department visit, hospitalization, or use of oral corticosteroids for asthma.Of the 4621 cohort patients, 231 initiated ICS monotherapy, and 97 initiated combination therapy. The hazard ratio (HR) for obesity was 1.67 (95% CI, 1.41-1.98). Compared with nonobese nonadherers, the HR for obese nonadherers was 1.54 (95% CI, 0.97-2.45); the HR for ICS monotherapy in obese and nonobese children was 0.85 (95% CI, 0.47-1.52) and 0.58 (95% CI, 0.37-0.91), respectively; and the HR for combination therapy in obese and nonobese children was 0.50 (95% CI, 0.13-1.89) and 0.46 (95% CI, 0.23-0.92), respectively.Obesity might be a determinant of shorter exacerbation-free time in children with asthma; however, we could not rule out a differential response to step 3 therapies by obesity status, potentially because of a lack of precision.