Angiogenesis is a complex process that involves the activation of endothelial cells through the triggering of several intracellular signaling pathways including those involving tyrosine phosphorylation. In the present study, we analyzed the angiogenic properties of two phosphotyrosyl phosphatase (PTP) inhibitors that are composed of a peroxovanadium core containing different ancillary ligands. In cell monolayer and 3D culture systems examined in this study, the administration of potassium bisperoxo(1,10-phenanthroline)oxovanadate(V) [bpV(phen)] or potassium bisperoxo(pyridine-2-carboxylato)oxovanadate(V) [bpV(pic)], but not oxovanadiums, interfered markedly with endothelial cell growth, organization, and terminal differentiation. This effect was dependent upon both the compound's dose and the nature of the ancillary ligand. Rat aortic ring assay showed a significant inhibition by low dose of bpV(phen) on cell migration. In addition, a chick embryo angiogenesis assay demonstrated that bpV(phen) is a potent inhibitor of angiogenesis. Among PTP inhibitors, bpV(phen) had powerful angiostatic properties at a low concentration.