In this study we investigate the costs and benefits of topical mesalazine combined with oral mesalazine therapy for active ulcerative colitis (UC), and once daily (OD ) mesalazine 2 grams versus twice daily (BID ) for maintaining UC remission. Two decision analytic models were constructed to evaluate treatment costs and quality-adjusted life years (QALYs) associated with mesalazine. The first model explored 4 g oral mesalazine in combination with 1 g topical mesalazine during active UC compared with 4 g oral mesalazine monotherapy for achieving clinical remission. The second model compared remission rates at one year for OD 2 g oral mesalazine compared with BID 1 g adjusted for compliance. All direct costs were obtained from established treatment costs in the Netherlands. The average cost of treatment to transition an active UC patient into remission using oral plus topical mesalazine or oral mesalazine monotherapy was v2207 (95% CI: v1402 to v3332) and v2945 (95% CI: v1717 to v4592), respectively. The annual average cost-saving of adding topical mesalazine delivered for four weeks during active UC was v738. The average annual costs of maintenance of remission with OD and BID therapy were v1293 (95% CI: v1062 to v1496) and v1502 (95% CI: v1262 to 1708), respectively with an annual average per person savings of v209. Topical mesalazine during acute UC flares results in lower costs due to reduced healthcare consumption attributed to faster symptom resolution. Furthermore, as a result of lower costs and modest QALY gains, maintenance therapy using OD mesalazine is the dominant treatment option if compared with BID mesalazine.