We used the aortic ring model of angiogenesis to investigate the role of β<sub>1</sub> and β<sub>3</sub> integrins in postangiogenic vascular survival in collagen and fibrin matrices. Confocal microscopy studies showed that both β<sub>1</sub> and β<sub>3</sub> integrins were expressed in endothelial cells and pericytes of sprouting neovessels. Antibody blocking experiments demonstrated that β<sub>1</sub> integrins but not β<sub>3</sub> integrins were required for angiogenic sprouting in collagen. Conversely, in fibrin, blockade of both integrins was needed to inhibit angiogenesis whereas treatment with either antibody alone was ineffective. Antibody-mediated blockade of β<sub>1</sub> but not β<sub>3</sub> integrins accelerated vascular regression in collagen. In contrast, both anti-β<sub>1</sub> and -β<sub>3</sub> integrin antibodies were required to promote neovessel breakdown in fibrin. These results demonstrate that angiogenic sprouting and postangiogenic neovessel survival in collagen are critically dependent on β<sub>1</sub> integrins. They also indicate that these processes involve a redundant repertoire of β<sub>1</sub> and β<sub>3</sub> integrins when angiogenesis occurs in fibrin. Thus, pharmacologic targeting of integrin receptors aimed at blocking neovessel formation and survival must be tailored to the specific extracellular matrix environment in which angiogenesis takes place.