Ionizing radiation (IR) is associated with thrombotic vascular occlusion. Thrombosis in malignancy predicts a poor clinical outcome. Tissue factor (TF) is the initiator of the extrinsic co-agulation system and induces thrombus formation. Our study examined whether IR induced TF expression and procoagulability in the myelomonocytic leukemia THP-1 cell model. We further investigated coordinated gene alterations associated with TF upregulation and IR-induced thrombogenicity. Gene expression profiling revealed IR to increase the expression of inflammatory and apoptosis-related pathways, contributing to TF upregulation and increased TF procoagulability on day 7 post IR. The upregulation of these pathways together with TF upregulation contributed to the increased thrombogenic potential of tissues post application of IR.