INTRODUCTION AND AIMS: The 5-aminosalicylates, especially mesalazine, are the first option in the treatment of mild-to-moderate ulcerative colitis (UC). High rates of remission induction and maintenance have been observed with the new multimatrix (MMX) mesalazine formulation, mainly in patients with distal disease. Our aim was to describe the real-world experience with MMX mesalazine in patients with UC at two tertiary care centers. MATERIALS AND METHODS: A retrospective cohort study was conducted that included 142 patients with confirmed UC diagnosis, analyzed in three study groups: 1) oral MMX mesalazine as monotherapy for remission induction, 2) oral MMX mesalazine as monotherapy for remission maintenance, and 3) oral MMX mesalazine plus topical therapy for remission induction. RESULTS: The frequency of clinical remission induction in group 1 was 80.3%, with biochemical remission of 74.2%. Group 2 had 100% clinical and biochemical remission maintenance. The frequency of clinical remission induction in group 3 was 88.6%, biochemical remission was 85.7%, and topical therapy was suspended in 87.3% at the end of follow-up. No adverse events were documented. CONCLUSIONS: There were high percentages of clinical and biochemical remission in the two corresponding study groups and topical therapy was suspended in the majority of patients in ashort follow-up period.