The intracellular signaling mechanisms underlying postnatal angiogenesis are incompletely understood.Herein we show that Grb-2-associated binder 1 (Gab1) plays a critical role in ischemic and VEGF-induced angiogenesis.Endothelium-specific Gabl knockout (EGKO) mice displayed impaired angiogenesis in the ischemic hindlimb despite normal induction of VEGF expression.Matrigel plugs with VEGF implanted in EGKO mice induced fewer capillaries than those in control mice.The vessels and endothelial cells (ECs) derived from EGKO mice were defective in vascular sprouting and tube formation induced by VEGF.