BACKGROUND Poor adherence with prescribed asthma medication is a major barrier to positive treatment outcomes. This study was designed to determine the effect of a once-daily administration of mometasone furoate administered via a dry powder inhaler (MF-DPI) on treatment adherence compared with a twice-daily administration. METHODS This was a 12-week open-label study designed to mimic an actual clinical setting in patients >or=12 years old with mild-to-moderate persistent asthma. Patients were randomized to receive MF-DPI 400 microg once-daily in the evening or MF-DPI 200 microg twice-daily. Adherence was assessed primarily using the number of actual administered doses reported from the device counter divided by the number of scheduled doses. Self-reports were also used to determine adherence. Health-related quality of life, healthcare resource utilization, and days missed from work or school were also reported. RESULTS 1233 patients were randomized. The mean adherence rates, as measured by the automatic dose counter, were significantly better (P < 0.001) with MF-DPI 400 microg once-daily in the evening (93.3%) than with MF-DPI 200 microg twice-daily (89.5%). Mean adherence rates based on self-reports were also significantly better (P < 0.001) with MF-DPI 400 microg QD PM (97.2%) than with MF-DPI 200 microg twice-daily (95.3%). Adherence rates were lower in adolescents (12-17 years old). Health-related quality of life improved by 20% in patients using MF-DPI once-daily in the evening and by 14% in patients using MF-DPI twice-daily. Very few (<8%) patients missed work/school. CONCLUSIONS Mean adherence rates were greater with a once-daily dosing regimen of MF-DPI than with a twice-daily dosing regimen.This trial was completed prior to the ISMJE requirements for trial registration.