Abstract Background With the goal of effective and early prevention and detection of medication-related adverse effects, an explosion of technological advances is taking place. However, none of these systems are currently intelligent enough to ensure safe prescribing of treatments on their own. Purpose To design and integrate clinical decision rules (CDR) to increase the safety of immunosuppressive treatments in patients with inflammatory bowel disease (IBD) into an electronic prescribing assistance software (HIGEA). Methods This is a descriptive study conducted in a tertiary university hospital in Madrid (Spain). 1. We reviewed the technical product information sheet of the immunomodulatory drugs used in the treatment of patients with IBD and the current recommendations and clinical practice guidelines on the management of IBD. 2. The CDR were developed within a multidisciplinary team of physicians and pharmacists by integrating data from pharmacogenetics, microbiology, biochemistry, immunology and haematology laboratories, the electronic medical record and the electronic prescribing programme. 3. Integration was performed using a standard language (HL7). Results The technical product information sheet of 33 immunomodulatory drugs (19 biological therapies, 6 small molecules and 8 traditional disease-modifying drugs) and the clinical practice guidelines for the treatment of IBD of the European Crohn's and Colitis organisation (ECCO) and the Spanish working group on Crohn's disease and ulcerative colitis (GETECCU) were reviewed. A total of 169 CDR were developed: 2 related to pharmacogenetics laboratory values, 26 to microbiology, 38 to biochemistry, 24 to immunology, 42 to haematology, 28 to clinical history and 9 related to concomitant use of other drugs. Of the 169 CDR, 50 (29.58 %) were related to screening prior to initiation of immunosuppressive treatment, 10 (5.92%) to drug interactions and 109 (64.5%) related to clinical conditions requiring adjustment or discontinuation of immunosuppressive treatment. Conclusion The incorporation of personalised clinical rules into the medical prescription and pharmaceutical validation process will allow the selection of patients in whom there could be a safety problem with immunosuppressive treatment, increasing the percentage of early detected and avoided adverse events. Future steps will be to evaluate the impact of the implementation of the CDR tool on increasing safety, reducing healthcare costs and improving patient health outcomes.