Background/Aims: A once-daily (OD) regimen of 5-aminosalicylic acid (5-ASA) was easier to comply with than a divided daily (DD) regimen, and that treatment efficacy for ulcerative colitis (UC) was not affected by the dosing regimen. This study evaluated treatment adherence of OD and DD dosing in the Korean UC patients. Methods: This study was a prospective, multicenter, randomized trial. UC patients were enrolled who have been in remission for more than 3 months. Patients were randomly assigned to the OD or DD group in a 1:1 ratio. The primary endpoint was adherence rate measured by tablet counts and self-reported adherence rate at 3, 6, 9, and 12 months. The relapse rate was measured at 1 year. Results: Data from the 180 patients who were randomized were analyzed. Both self-reported adherence rate and adherence rate measured by tablet counts were not different at every points, including 1 year. The patients’ satisfaction of the OD group was higher than that of the DD group (P<0.001). At 1 year, 91.2% and 95.5% of patients in the OD group and DD group had maintained clinical remission, respectively (P=0.37). Conclusions: The adherence rates were not different between the OD group and DD group. The patients’ satisfaction was higher in the OD group than in the DD group. 5-ASA OD dosing might have the same effect as DD for the maintenance of UC remission. (Intest Res 2019;17:349-356)