Platelet adhesion to subendothelial types I and III collagens exposed upon vascular injury plays a crucial role in hemostasis and thrombosis. We previously identified a KOGEOGPK sequence (O for hydroxyproline) within type III collagen interacting with platelets, and demonstrated a strong inhibitory effect of the KOGEOGPK peptide on human platelet interactions with type III collagen in vitro. In the present study, we tested the antithrombotic effect of KOGEOGPK in vivo. In a mouse model of pulmonary thromboembolism induced by intravenous injection of type III collagen and epinephrine, prior administration of 80 mg/kg KOGEOGPK reduced by 50% the size of thrombi embolized in lungs, compared to vehicle-treated mice (p<0.0001). In a mouse model of photochemically induced lesion of caecum venules and arterioles, intravenous injection of 80 mg/kg KOGEOGPK decreased by 76% the occurrence of arteriole occlusion 45 min after vascular injury (p<0.05). A moderate antithrombotic effect of KOGEOGPK was also observed in the injured venules. In addition, intracardiac injection of KOGEOGPK had no effect on the tail bleeding time. These findings demonstrate a substantial contribution of platelet interactions with the type III collagen-related KOGEOGPK sequence in thrombus formation in vivo with preferential involvement in arterial thrombosis.