OBJECTIVES: Compare oral 5-aminosalicylic acid (5-ASA) treatment persistence and adherence in patients with mild/moderate ulcerative colitis (UC). METHODS: IMS LifeLink™ Health Plan claims data were analyzed to identify patients ≥18 years with ≥1 UC diagnosis (ICD-9-CM: 556.x) and had ≥1 prescription for 5-ASA (sulfasalazine, Multi-Matrix System mesalamine [MMX], balsalazide disodium, mesalamine delayed release [MDR]) during 2007-2011.  Patients were continuously enrolled in the 6-month pre- and 12-month post-initiation period.  5-ASA treatment persistence and adherence according to the initial prescription filled (index medication) were compared.  Persistence was defined as the duration between initiation and discontinuation of therapy with a permissible gap <60 days, and analyzed using Kaplan-Meier survival analysis.  Persistence rates at month 12 were calculated.  Adherence was measured by medication possession ratio (MPR) for index drug, and proportion of days covered (PDC) for any 5-ASA.  Analysis of covariance was used to compare MPR and PDC across index medication.  Covariates included age, gender, insurance, residential region, comorbidities at index date, and use of immunosuppressive/biologic agents, rectal form of 5-ASA and access to specialist care post 12-month index date. RESULTS: A total of 5245 patients met selection criteria, 59% were on MDR, 17% MMX, 13% sulfasalazine, and 11% balsalazide.  The median persistence days ranged from 151 [sulfasalazine] to 221 [MMX] days, P=0.001).  Persistence rates at month 12 was highest for MMX (28%) compared to other 5-ASAs (24% MDR, 23% balsalazide, and 20% sulfasalazine, respectively, logrank P<0.001).  Mean adjusted MPR/PDC ± standard error was significantly higher in the patients on MMX (0.48±0.02/0.53±0.02) than that of patients on other 5-ASAs (0.43±0.01/0.50±0.01 [MDR], 0.43±0.02/0.49±0.02 [balsalazide], and 0.39±0.02/0.47±0.02 [sulfasalazine], P<0.01/P<0.04). CONCLUSIONS: Patients on once-daily MMX were significantly more persistent and adherent with UC treatment than those on other 5-ASA index drugs although persistence and adherence with oral 5-ASAs in UC patients were suboptimal.