Pharmacogenomics is the study of genetic variability affecting an individual’s response to a drug. Its use allows personalized medicine and reduction in ‘trial and error’ prescribing leading to more efficacious, safer and cost-effective drug therapy. The U-PGx consortium will investigate a pre-emptive genotyping approach (that is: multiple pharmacogenomic variants are collected prospectively and embedded into the patients’ electronic record) of a panel of important pharmacogenomic variants as a new model of personalised medicine. To meet this goal we combine existing pharmacogenomics guidelines and novel health IT solutions. Implementation will be conducted at a large scale in seven existing European health care environments and accounts for the diversity in health system organisations and settings. Feasibility, health outcome and cost-effectiveness will be investigated. We will formulate European strategies for improving clinical implementation of pharmacogenomics based on the findings of this project.