Summary Objective: The objective of this study is to estimate the amount of severe drug-drug interaction warnings per medical specialist group triggered by prescribed drugs of a patient before and after the introduction of a nationwide eMedication system in Austria planned for 2015. Methods: The estimations of interaction warnings are based on patients’ prescriptions of a single health care professional per patient, as well as all patients’ prescriptions from all visited health care professionals. We used a research database of the Main Association of Austrian Social Security Organizations that contains health claims data of the years 2006 and 2007. Results: The study cohort consists of about 1 million patients, with 26.4 million prescribed drugs from about 3,400 different health care professionals. The estimation of interaction warnings show a heterogeneous pattern of severe drug-drug-interaction warnings across medical specialist groups. Conclusion: During an eMedication implementation it must be taken into consideration that different medical specialist groups require customized support. Citation: Rinner C, Sauter SK, Neuhofer LM, Edlinger D, Grossmann W, Wolzt M, Endel G, Gall W. Estimation of severe drug-drug interaction warnings by medical specialist groups for Austrian nationwide eMedication. Appl Clin Inf 2014; 5: 603–611 http://dx.doi.org/10.4338/ACI-04-RA-0030