Description: Background: Upon admission to a hospital patients' medications are frequently switched to alternativedrugs compiled in so called hospital drug formularies. This substitution process is a laboriousand error-prone task which should be supported by sophisticated electronic tools. Wedeveloped a computerised decision support system and evaluated benefit and potential harmassociated with its use. Methods: Based on a multi-step algorithm we identified drug classes suitable for exchange, definedconversion factors for therapeutic interchange, built a web-based decision support system,and implemented it into the computerised physician order entry of a large university hospital.For evaluation we compared medications manually switched by clinical pharmacists with theresults of automated switching by the newly developed computer system and optimised thesystem in an iterative process. Thereafter the final system was tested in an independent set ofprescriptions. Results: After iterative optimisation of the logical framework the tool was able to switch drugs topharmaceutical equivalents and alternatives; in addition, it contained 21 different drug classesfor therapeutic substitution. In this final version it switched 91.6% of 202 documentedmedication consultations (containing 1,333 drugs) automatically, leaving 8.4% for manualprocessing by clinical professionals. No incorrect drug switches were found. Conclusion: A large majority (〉90%) of drug switches performed at the interface between primary andtertiary care can be handled automatically using electronic decision support systems,indicating that medication errors and workload of healthcare professionals can beconsiderably reduced.