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For the correct interpretation of test results, it is important to be aware of drug-laboratory test interactions (DLTIs). If DLTIs are not taken into account by clinicians, erroneous interpretation of test results may lead to a delayed or incorrect diagnosis, unnecessary diagnostic testing or therapy with possible harm for patients. A DLTI alert accompanying a laboratory test result could be a solution. The aim of this study was to test a multicentre proof of concept of an electronic clinical decision support system (CDSS) for real-time monitoring of DLTIs. CDSS was implemented in three Dutch hospitals. So-called 'clinical rules' were programmed to alert medical specialists for possible DLTIs based on laboratory test results outside the reference range in combination with prescribed drugs. A selection of interactions from the DLTI database of the Dutch society of clinical chemistry and laboratory medicine were integrated in 43 clinical rules, including 24 tests and 25 drugs. During the period of one month all generated DTLI alerts were registered in the laboratory information system. Approximately 65 DLTI alerts per day were detected in each hospital. Most DLTI alerts were generated in patients from the internal medicine and intensive care departments. The most frequently reported DLTI alerts were potassium-proton pump inhibitors (16%), potassium-beta blockers (11%) and creatine kinase-statins (11%). This study shows that it is possible to alert for potential DLTIs in real-time with a CDSS. The CDSS was successfully implemented in three hospitals. Further research must reveal its usefulness in clinical practice. [ABSTRACT FROM AUTHOR]