Fibrosis represents the end-stage of a broad range of disorders affecting organ function. These disorders are often associated with aberrant angiogenesis, but whether vascular abnormalities during fibrosis are characterized by excessive or diminished neo-vascularization remains questionable. Strikingly, activation of the coagulation cascade is frequently observed in association with the progression of fibroproliferative disorders. As we recently showed that coagulation factor (F)Xa induced fibrotic responses in fibroblasts, we hypothesized that FXa might indirectly induce angiogenesis by triggering fibroblasts to secrete proangiogenic factors. In the present study, we show that although FXa induces p42/44 MAP Kinase phosphorylation in endothelial cells, it has no direct effect on endothelial cell proliferation, protein synthesis and tube formation. In contrast, conditioned medium of fibroblasts stimulated with FXa enhanced endothelial cell proliferation, extra cellular matrix synthesis, wound healing and endothelial tube formation. FXa induced VEGF production by fibroblasts and a VEGF neutralizing antibody blocked the indirect effect of FXa on proliferation and realignment of endothelial cells identifying VEGF as a crucial player in angiogenesis during coagulation factor-induced fibrosis. Overall, our results establish a link between the coagulation cascade and angiogenesis during fibrosis.