BACKGROUND: Recent evidence suggests that the use of leukotriene receptor antagonists (LTRAs) in addition to inhaled corticosteroids (ICSs) in asthmatic patients provides comparable benefits to the addition of long-acting β-agonists (LABAs) to ICSs. OBJECTIVE: We sought to compare, in a unified framework, adherence, outcomes, and costs associated with ICS+LTRA versus ICS+LABA as step-up therapies for asthma. METHODS: Using the administrative databases of British Columbia, Canada (years 1997-2007), we created a propensity score-matched sample of asthmatic patients (12-45 years old) receiving ICS+LTRA therapy versus ICS+LABA therapy after a period of monotherapy with an ICS. We compared the outcomes using 2 analyses: an intention-to-treat (ITT) analysis that followed subjects for a fixed period of 2 years and an uninterrupted treatment analysis that followed subjects for as long as they continuously dispensed their index medications. RESULTS: The matched cohort consisted of 1032 subjects in each group (mean age at entry, 27.4 years; 52.5% female). Adherence, which was defined as the proportion of days covered, was higher in the ICS+LABA group compared with the ICS+LTRA group. In both the ITT and uninterrupted treatment analyses, use of ICS+LTRA therapy was associated with more asthma-related outpatient visits, asthma-related medication dispensations, and dispensation of reliever medications. Dispensation of oral corticosteroids and rate of asthma exacerbations were higher in the ICS+LTRA group in the uninterrupted treatment analysis but not in the ITT analysis. CONCLUSIONS: In a real-world clinical setting subjects were more adherent to ICS+LABA therapy than ICS+LTRA therapy. ICS+LABA therapy seems to be more effective than ICS+LTRA therapy in the management of asthma, regardless of adherence.