OBJECTIVES: The main objective is to assess the economic implications of replacing standard oral corticosteroid treatment with budesonide MMX^® for induction of remission in mild-to-moderate ulcerative colitis (UC). Steroid-associated adverse events (AEs) provoke high treatment costs and generate significant expenditures for the public payer. Budesonide MMX^® was found to have favorable safety profile due to lower bioavailability than systemic steroids. According to these findings budesonide MMX allows for even 7-fold reduction in the risk of adverse events. Therefore, its potential to decrease AE related treatment cost requires further investigation. METHODS: Electronic databases (Medline, Embase and The Cochrane Library) were systematically searched for clinical trials to compare budesonide MMX^® versus other steroids and to assess long-term side effects of steroid use. The economic burden of steroid-related side effects including prevention and treatment costs was evaluated in an economic model. The risk of side effects was fitted proportionally to the cumulative dose of steroids. The costs of adverse events corresponded to the use of all resources being determined by Polish clinical practice as well as Polish and international guidelines for the treatment of all specific AEs. RESULTS: Costs of nine most frequent and cost-intensive serious steroid-related side effects like osteoporosis, glaucoma, cataract, hypertension, type 2 diabetes, myopathy, neuropathy, depression and vein thrombosis were estimated. The cumulative projected 20-year treatment cost of all selected side effects was 2 310 € vs 425 € per patient treated with standard oral corticosteroids and with budesonide MMX^®, respectively. The results were robust under sensitivity testing. CONCLUSIONS: Treatment of steroid-related side effects constitutes significant long-term cost of medical care. Budesonide MMX^® could allow for substantial cost reduction. The favorable safety profile outcomes has delivered strong evidence of budesonide MMX^® being cost-effective compared with standard steroid therapy for induction of remission in mild-to-moderate UC.