Background: Hematopoietic acute radiation syndrome (H-ARS) occurs in individuals that are exposed to high levels of radiation over a short period of time. The destruction of bone marrow leads to pancytopenia, which increases the incidence of infections and accounts for the majority of morbidity and mortality. Sargramostim (yeast-derived rhGM-CSF) is a leukocyte growth factor that promotes differentiation, maturation and activation of granulocytes, monocytes and macrophages. Methods: We evaluated the efficacy of repeat administrations of sargramostim (7 μg/kg/day) in a blinded, GLP study in total body irradiated non-human primates (NHPs) when administered 48 h post-irradiation with minimal supportive care (e.g., no blood products or individualized antibiotics). The primary objective was to assess the efficacy of sargramostim versus vehicle on mortality rate at Day 60 in irradiated male and female NHPs at LD50-60/60 (n=36/group). Secondary objectives included the efficacy of sargramostim on overall survival and its effect on hematology parameters. The study included an exploratory arm of male and female NHPs that were irradiated at a LD70-80/60(n= 18/group) and received the same treatments. Results: Sargramostim decreased the mortality rate at Day 60 by 36% in the LD50-60/60 group (p=0.0018) and by 44% in the LD70-80/60 group (p=0.0076). Additionally, neutrophil, platelet, lymphocyte, and white blood cell levels in survivors demonstrated accelerated recovery in the sargramostim-treated NHPs in the LD50-60/60 and LD70-80/60 groups. Conclusion: Treatment with sargramostim (7 μg/kg/day) beginning at 48 h, in the absence of blood products and individualized antibiotics, suggests that the use of sargramostim is a viable therapeutic strategy for H-ARS in a mass casualty event. Funding: This project has been funded in whole or in part with Federal funds from the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under Contract No. HHSO100201300005I. Disclosures Clayton: Sanofi Genzyme: Employment. Charpentier:Sanofi: Employment. LaCasse:Sanofi Genzyme: Employment. Khan-Malek:Sanofi: Employment. Keutzer:Sanofi Genzyme: Employment.