Few reports have investigated the efficacy of using inhaled corticosteroid (ICS)-containing inhalers to treat patients with asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO). To investigate the effect of ICS treatment on patients with ACO using 5 sets of diagnostic criteria. Patients with stable COPD enrolled in the Korean COPD subgroup study cohort were assessed for asthma overlap. Patients who were prospectively followed up for 1 year were included in an exacerbation analysis. Among 1067 patients with COPD, 138 (12.9%), 32 (3.0%), 171 (16%), 221 (20.7%), and 264 (24.7%) were classified as having ACO by the Global Initiative for Asthma (GINA)/Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, the American Thoracic Society roundtable criteria, the modified Spanish criteria, the updated Spanish criteria, and specialists' diagnoses, respectively. According to the specialists' diagnoses, the ACO exacerbation rate was higher than that for COPD alone (incidence rate ratio IRR = 1.65; P < .01), even after adjustment for covariates. Patients with ACO who used ICSs experienced less exacerbation, according to the specialists' diagnoses and the GINA/GOLD criteria (IRR = 0.55, P = .026; IRR = 0.69, P = .046, respectively). The only factor associated with a decrease in ACO exacerbation after ICS use was a blood eosinophil count of ≥300 cells/μL (IRR = 0.52, P = .03) irrespective of the diagnosis of ACO by any set of criteria. This study suggests that ICS treatment can decrease the risk of exacerbation in patients with ACO, and that a blood eosinophil count of ≥300 cells/μL can predict the response to ICS treatment.