BACKGROUND AND OBJECTIVES: D-negative red cells are transfused to D-negative females of childbearing potential (CBP) to prevent haemolytic disease of the foetus and newborn (HDFN). Transfusion of low-titre group O whole blood (LTOWB) prehospital is gaining interest, to potentially improve clinical outcomes and for logistical benefits compared to standard of care. Enhanced donor selection requirements and reduced shelf-life of LTOWB compared to red cells makes the provision of this product challenging. MATERIALS AND METHODS: A universal policy change to the use of D-positive LTOWB across England was modelled in terms of risk of three specific harms occurring: risk of haemolytic transfusion reaction now or in the future, and the risk of HDFN in future pregnancies for all recipients or D-negative females of CBP. RESULTS: The risk of any of the three harms occurring for all recipients was 1:14 × 103 transfusions (credibility interval [CI] 56 × 102 -42 × 103 ) while for females of CBP it was 1:520 transfusions (CI 250-1700). The latter was dominated by HDFN risk, which would be expected to occur once every 5.7 years (CI 2.6-22.5). We estimated that a survival benefit of ≥1% using LTOWB would result in more life-years gained than lost if D-positive units were transfused exclusively. These risks would be lower, if D-positive blood were only transfused when D-negative units are unavailable. CONCLUSION: These data suggest that the risk of transfusing RhD-positive blood is low in the prehospital setting and must be balanced against its potential benefits.