Limited response to single agent anti-PD-1 antibody in AML suggests that co-inhibitory molecules other than PD-1 may induce immune evasion in AML. Programmed Death-1 Homolog (PD-1H, VISTA) is a novel co-inhibitory molecule, highly expressed on myeloid cells and T cells. Interestingly, the Cancer Genome Atlas revealed that PD-1H is highly expressed in AML. We performed flow cytometric analyses demonstrating that PD-1H is expressed on AML blasts in addition to immune cells such as myeloid cells and T cells. To determine if AML surface PD-1H induces immune evasion, we transplanted C1498FF cells (murine AML cells, engineered to express luciferase) transduced with PD-1H expression lentivirus (C1498FF-PD-1H) or with control lentivirus (C1498FF-mock) in syngeneic B6 mice to assess AML proliferation in vivo using a bioluminescence assay. Interestingly, in vivo proliferation of C1498FF-PD-1H cells was significantly faster than C1498FF-mock cells. While AML surface PD-1H induces immune evasion, PD-1H has been reported to be expressed in host immune cells, including T cells and myeloid cells. Thus, we further hypothesized that PD-1H on host immune cells induces immune evasion in AML. C1498FF cells were transplanted in PD-1H knockout (KO) or wild-type B6 mice to assess in vivo proliferation using a bioluminescence. The genetic deletion of PD-1H in host immune cells (KO mice), especially myeloid specific PD-1H deletion confers significant anti-leukemic effect, compared with wild-type control. Together, our data suggest that PD-1H is highly expressed in human AML, can induce immune evasion in a murine model of AML and can be an important immunotherapeutic target in AML.