Background Each year blood transfusions save millions of lives. However, under current blood-matching practices sensitisation to non-self antigens is an unavoidable adverse side effect and is considered a price worth paying for life saving support. We describe a universal donor typing platform that can be adopted by blood services worldwide to facilitate a universal extended matching policy and reduce sensitisation rates. Methods We present a genetic test capable of simultaneously typing all clinically relevant red blood cell (RBC), platelet (HPA) and leukocyte (HLA) antigens. Validation was performed using samples from 7,984 blood donors. We illustrated the usefulness of the platform by analysing “real world” data from sensitised patients with multiple RBC alloantibodies. Findings Genotyping results demonstrated concordance of 99•91%, 99•97% and 99•03% with RBC, HLA and HLA clinically validated results in 89,371, 3,016 and 9,289 comparisons respectively. Genotyping increased the total number of antigen typing results available from 110,980 to over 1•2 million. Denser typing allowed identification of 2•6 times more compatible donors to serve 3,146 patients with multiple RBC alloantibodies, providing at least one match for 176 individuals for whom previously no blood could be found amongst the same donors. We used the data to provide life-saving transfusion support to a 24-year old female patient with myelodysplastic syndrome and multiple RBC alloantibodies. Interpretation This affordable genotyping technology provides an opportunity to implement a policy of genomics-based precision matching of blood, which avoids sensitisation. / NHS Blood and Transplant, National Institute for Health Research, Health Data Research UK and Sanquin.