BACKGROUND: The Los Angeles Development and Rapid Operationalization of Prehospital Blood (LA-DROP) pilot will protocolize prehospital administration of low titer O-positive whole blood (LTO + WB) to patients with hemorrhagic shock in Los Angeles County (LAC). We sought to quantify the risk of death from hemolytic disease of the fetus and newborn (HDFN) associated with RhD-negative alloimmunization in females of childbearing potential (FCPs) as a result of LA-DROP. STUDY DESIGN AND METHODS: Retrospective data from LAC EMS databases were used in combination with estimates from published literature to assign probability distributions to each event in the sequence required for a transfusion of LTO + WB to result in a death from HDFN. Markov chain Monte Carlo simulation was used to derive risk estimates. RESULTS: We estimated that the proposed prehospital transfusion strategy would result on average in one death from HDFN for every 10,000 transfusions in the overall population (95% confidence interval [CI] 6000-25,000) and for every 1800 transfusions in FCPs (95% CI 1000-4300). Based on the projected annual volume of transfusions under LA-DROP, this would result in one death due to HDFN approximately every 26 years (95% CI 15-64). DISCUSSION: The estimated per-transfusion risk of HDFN is similar to previously published work from other populations. The estimated frequency of deaths from HDFN associated with LA-DROP is lower than some previously published calculations, likely because of narrower eligibility criteria for transfusion.