To　date　only　four　recombinant　growth　factors,　including　Filgrastim　(rhG-CSF),　have　been　approved　by　FDA　as　radiomitigators　to　ameliorate　hematopoietic　acute　radiation　syndrome　(H-ARS).　These　approved　agents　are　not　stable　under　room-temperature,　needing　to　be　stored　at　2–8　°C,　and　would　not　be　feasible　in　a　mass　casualty　scenario　where　rapid　and　cost-effective　intervention　is　crucial.　Delta-tocotrienol　(δ-T3H),　the　most　potent　G–CSF–inducing　agent　among　vitamin　E　isoforms,　exhibited　efficiency　and　selectivity　on　G-CSF　production　in　comparison　with　TLR　and　STING　agonists　in　mice.　Five-dose　δ-T3H　was　utilized　as　the　optimal　therapeutic　regimen　due　to　long-term　G-CSF　production　and　the　best　peripheral　blood　(PB)　recovery　of　irradiated　mice.　Comparable　with　rhG-CSF,　sequential　administration　of　δ-T3H　post-irradiation　improved　hematologic　recovery　and　accelerated　the　regeneration　of　hematopoietic　stem　cells　(HSCs)　and　hematopoietic　progenitor　cells　(HPCs)　in　the　bone　marrow　(BM)　and　spleen　of　6.5Gy　irradiated　mice;　and　consistently　enhanced　repopulation　of　BM-HSCs.　In　4.0Gy　irradiated　nonhuman　primates,　δ-T3H　exhibited　comparable　efficacy　as　rhG-CSF　to　promote　PB　recovery　and　colony-formation　of　BM-HPCs.　Altogether,　we　demonstrated　that　sequential　administration　of　delta-tocotrienol　ameliorates　radiation-induced　myelosuppression　in　mice　and　non-human　primates　through　inducing　G-CSF　production,　indicated　δ-T3H　as　a　promising　radiomitigator　for　the　management　of　H-ARS,　particularly　in　a　mass　casualty　scenario.　©　2024　Elsevier　Inc.