BACKGROUND: Real-world evidence on the effectiveness of maintenance and reliever therapy (MART) using inhaled corticosteroids plus long-acting beta-2 agonist (ICS-LABA) is sparse. OBJECTIVE: This study aimed to evaluate the clinical effectiveness of MART (ICS-formoterol) by comparing its effectiveness with that of ICS-LABA plus as-needed short-acting beta-2 agonist (SABA) in adult asthmatics. METHODS: We retrospectively retrieved data from the medical records of the Ajou University Medical Center, Korea, to compare clinical outcomes between patients treated with MART (the MART group) and those treated with ICS-LABA plus SABA (the non-MART group). Propensity score matching was performed and hazard ratios (HRs) with 95% confidence intervals were calculated using the Cox proportional hazards model. Severe asthma exacerbation (SAEx) was the primary end point, and asthma exacerbation (AEx), hospitalization, and pneumonia were secondary end points. Corticosteroid requirement was also analyzed. RESULTS: After propensity score matching, the MART and the non-MART groups included 231 and 512 adult asthmatics, respectively. The risk of SAEx and AEx was significantly lower in the MART group than in the non-MART group (HR [95% CI] 0.39 [0.18-0.77] and 0.61 [0.37-0.99], respectively). There was no significant difference in hospitalization and pneumonia risk between the 2 groups (HR [95% CI] 0.88 [0.55-1.37] and 0.63 [0.03-4.51], respectively). Corticosteroid requirements were lower in the MART group than in the non-MART group (median [interquartile range], 190.0 [97.9-420.0] and 411.0 [143.0-833.0] mg/person-year, respectively; P < .01). CONCLUSIONS: The MART strategy of ICS-formoterol was associated with lower risk of AEx and reduced corticosteroid requirement.