Background and Aims Interventions to improve adherence to medication may be more effective if tailored to the individual, addressing adherence-related beliefs about treatment and overcoming practical barriers to daily use. We evaluated whether an algorithm, tailoring support to address perceptual and practical barriers to adherence, reduced barriers and was acceptable to patients with inflammatory bowel disease [IBD]. Methods Participants with IBD, prescribed azathioprine and/or mesalazine, were recruited via patient groups, social media, and hospital clinics and allocated to Intervention or Control Groups. The online intervention comprised messages tailored to address beliefs about IBD and maintenance treatment and to provide advice on overcoming practical difficulties with taking regular medication. The content was personalised to address specific perceptual and practical barriers identified by a pre-screening tool. Validated questionnaires assessed barriers to adherence and related secondary outcomes at baseline and at 1 and 3 months of follow-up. Results A total of 329 participants were allocated to the Intervention [n = 153] and Control [n = 176] Groups; just under half [46.2%] completed follow-up. At 1 and 3 months, the Intervention Group had significantly fewer concerns about IBD medication [p ≤0.01]; and at three months, fewer doubts about treatment necessity, fewer reported practical barriers, and higher reported adherence [p <0.05]. Relative to controls at follow-up, the Intervention Group were more satisfied with information about IBD medicines, and viewed pharmaceuticals in general more positively. Questionnaires, interviews, and intervention usage indicated that the intervention was acceptable. Conclusions Personalised adherence support using a digital algorithm can help patients overcome perceptual barriers [doubts about treatment necessity and medication concerns] and practical barriers to adherence.