The α2β1 integrin serves as a receptor for collagens, laminin, and several other nonmatrix ligands. Many studies have suggested that the α2β1 integrin is a critical mediator of platelet adhesion to collagen within the vessel wall after vascular injury and that the interactions of the platelet α2β 1 integrin with subendothelial collagen after vascular injury are required for proper hemostasis. We have used the α2β 1 integrin-deficient mouse to evaluate the contributions of the α2β1 integrin in 2 in vivo models of thrombosis. Studies using a model of endothelial injury to the carotid artery reveal that the α2β1 integrin plays a critical role in vascular thrombosis at the blood-vessel wall interface under flow conditions. In contrast, the α2β1 integrin is not required for the formation of thrombi and pulmonary emboli following intravascular injection of collagen. Our results are the first to document a critical in vivo role for the α2β1 integrin in thrombus formation at the vessel wall under conditions of shear following vascular injury.