This is a prospective comparison study between once a day and 3 divided doses of mesalazine in Ulcerative colitis conducted in a tertiary care hospital in Kerala, India. The study was conducted for a period of 18 months from February 2014 to July 2015. The purpose of this study was to find the efficacy and safety between the two different dosing schedules.A total of 60 patients were evaluated of this, 31 patients were in OD treatment group and 29 patients were assigned in the TID group. This study has demonstrated a clinical remission of 61.3% patients in the O.D group and 62.1% in TID. Endoscopic remission was achieved in 71% of patients in O.D group compared to 62.1% in the TID group at the end of 8th week and a Histological remission of 74.2% patients in OD group and 58.6 in the TID group.Patients in O.D group had a significant relief of abdominal pain compared to the TID group (p 0.020). A significant reduction in stool frequency was also seen in OD group (p 0.011).No patients in OD or TID group reported any serious adverse events.