BACKGROUND: Mesalamine is the recommended first-line treatment for inducing and maintaining remission in mild-to-moderate ulcerative colitis (UC). However, adherence in real-world settings is frequently suboptimal. Encouraging collaborative patient-provider relationships may foster better adherence and patient outcomes. AIM: To quantify the association between patient participation in treatment decision-making and adherence to oral mesalamine in UC. METHODS: We conducted a 12-month, prospective, non-interventional cohort study at 113 gastroenterology practices in Germany. Eligible patients were aged >/= 18 years, had a confirmed UC diagnosis, had no prior mesalamine treatment, and provided informed consent. At the first visit, we collected data on demographics, clinical characteristics, patient preference for mesalamine formulation (tablets or granules), and disease knowledge. Self-reported adherence and disease activity were assessed at all visits. Correlation analyses and logistic regression were used to examine associations between adherence and various factors. RESULTS: Of the 605 consecutively screened patients, 520 were included in the study. The median age was 41 years (range: 18-91), with a male-to-female ratio of 1.1:1.0. Approximately 75% of patients reported good adherence at each study visit. In correlation analyses, patient participation in treatment decision-making was significantly associated with better adherence across all visits (P = 0.04). In the regression analysis at 12 months, this association was evident among patients who both preferred and received prolonged-release mesalamine granules (odds ratio = 2.73, P = 0.001). Patients reporting good adherence also experienced significant improvements in disease activity over 12 months (P < 0.001). CONCLUSION: Facilitating patient participation in treatment decisions and accommodating medication preferences may improve adherence to mesalamine. This may require additional effort but has the potential to improve long-term management of UC.