Inhaled glucocorticosteroids are usually administered in two equal daily doses. To simplify the method of treatment, once-daily administration has been used. However, little information regarding whether once-daily treatment can sufficiently control airway inflammation is available. We aimed to investigate whether once-daily administration of inhaled glucocorticosteroids can control airway inflammation.Twenty-four well-controlled asthma patients were enrolled in a randomized crossover trial to compare the efficacies of once-daily and twice-daily administration of inhaled glucocorticosteroids. Initially, the patients were randomly assigned to receive either once-daily or twice-daily administration for 16 weeks. After an 8-week washout period, patients who originally received twice-daily administration were assigned to once-daily administration for 16 weeks and vice versa. We assessed the changes in the forced expiratory volume in 1s, morning and evening peak expiratory flows, asthma symptoms, health-related quality of life and fractional exhaled nitric oxide levels.Patients with once-daily administration showed the same level of clinical control and lung functions as patients receiving twice-daily administration. There was no difference in the fractional exhaled nitric oxide levels between the beginning and end of the twice-daily treatment (35.69 and 33.23ppb, respectively). In contrast, the fractional exhaled nitric oxide level was significantly higher at the end of the once-daily treatment (33.87 and 39.38ppb, respectively, p< 0.001).Although once-daily administration is sufficient for clinical control of asthma, it might not control airway inflammation sufficiently.