OBJECTIVES: The aim of this study was to assess adherence and persistence to mesalamine treatment in ulcerative colitis (UC), and to evaluate the impact on health care resource utilization and cost from a Canadian health care system perspective.  METHODS: A retrospective prescription and medical claims analysis was conducted using a random sample of UC patients with no diagnosis of Crohn’s disease who were initiated on an oral mesalamine formulation from January 2005 to December 2009. Treatment adherence (medication possession ratio [MPR]) and persistence were calculated over a 1-year period after index prescription. To evaluate the economic impact of non-adherence and non-persistence, the number and all-cause costs of physician visits, emergency visits, and hospitalizations were estimated. Statistical comparisons, based on adherence and persistence, were made using the chi-square test for proportions and Student’s t-test or the F-test from one-way ANOVA for means. Statistical significance was p<0.05.  RESULTS: A sample of 1681 patients was obtained. The mean age of new oral mesalamine users was 55.3 years (SD=17.8), with a similar proportion of males and females. At month 12, 27.7% of patients had a MPR ≥80%, and 45.5% of patients were persistent on treatment.  Over the 12-month period, there was a statistically significant difference in overall health care resource utilization and all-cause costs in non-persistent ($4973.57) versus persistent ($3256.23) patients to UC medications (p<0.001, unadjusted), with hospitalizations as the major cost driver. Similar numeric differences were observed for overall health care costs associated with non-adherence versus adherence ($4357.70 versus $3758.81, p=0.277, unadjusted). CONCLUSIONS: Adherence and persistence to oral mesalamine for the treatment of UC was relatively poor in this patient cohort. Furthermore, patients who were non-persistent on therapy used more health care resources and were more costly during the 12-month observation period.