5-aminosalycilic acid (5-ASA) therapy is effective for maintaining remission in patients with ulcerative colitis (UC) and may also reduce colorectal cancer risk. However, medication non-adherence is a known barrier to the effectiveness of prescribed regimes and there is a lack of evidence about methods of improving adherence to 5-ASA treatment. This research programme addressed the hypothesis that adherence can be improved by a multi-faceted intervention tailored to individual patient needs. A qualitative study identified that important determinants of adherence to 5-ASA medication are: information provided, patient beliefs and the patient-clinician relationship. Adherence can change over time; the study highlighted the need for reinforcement and the fact that health care professionals have a crucial role to play in this dynamic. A cross-sectional study confirmed the difficulty of accurately assessing medication adherence. The two measures used (self-report and urine analysis) were not correlated, phi correlation 0.029 (p = 0.725). Logistic regression identified a significant association between self-reported non-adherence and: younger age [OR for increased age 0.954, 95% CI 0.932–0.976] and also doubts about personal need for medication (OR for BMQ – Specific Necessity scores 0.578, 95%CI 0.366–0.913). For non-adherence based on urine analysis, only South Asian ethnicity was independently associated with non-adherence (OR 2.940, 95%CI 1.303–6.638). A randomised controlled trial showed that a multi-faceted, tailored intervention (including an opportunity for patients to select reminder devices from a range offered) had a significant positive impact on maintaining adherence levels in the intervention group (p=0.001), with a 44% difference between adherence levels in the two groups at follow-up. Changes in questionnaire scores suggested a positive effect of the intervention on satisfaction with information (p<0.001). The intervention was feasible, and was acceptable to patients. The multi-faceted approach studied has potential for implementation in routine care for enhancing persistence with 5-ASA and thus improving patient outcomes.