We conducted this study to compare the efficacy and safety of once-daily mometasone furoate (MF) administered by dry powder inhaler (DPI) with once-daily budesonide (BUD)-DPI and placebo in patients with moderate persistent asthma previously using twice-daily inhaled corticosteroids. A total of 262 patients (> or = 12 years of age) with moderate persistent asthma were randomised to once-daily morning treatment with MF-DPI 440 microg (metered dose), BUD-DPI 400 microg (metered dose), or placebo in an eight-week, multicentre, placebo-controlled, double-blind, double-dummy study. The primary efficacy variable was percent change in FEV1 from baseline to endpoint (last evaluable visit). At endpoint, the percent change in FEV1 was significantly greater (p < 0.01) following treatment with MF-DPI 440 microg (8.9%) than with both BUD-DPI 400 microg (2.1%) and placebo (-3.9%). Secondary efficacy variables, including morning and evening peak expiratory flow rates, albuterol use, percentage of asthma symptom-free days, and physician-evaluated response to therapy were also significantly improved at endpoint in the MF-DPI group compared with both the placebo and BUD-DPI groups (p < 0.05). Both active treatments were well tolerated. In conclusion, once-daily treatment in the morning with MF-DPI 440 microg significantly improved pulmonary function and asthma control compared with morning administration of BUD-DPI 400 microg and placebo.