GPVI, a major platelet activation receptor for collagen and fibrin, is considered as a particularly promising safe antithrombotic target. In this study, we show that human GPVI is a receptor for fibrinogen. Full spreading of human platelets on fibrinogen is abolished in platelets from GPVI-deficient patients suggesting that fibrinogen activates GPVI. While mouse platelets fail to spread on fibrinogen, human-GPVI-transgenic mouse platelets show full spreading and increased Ca2+ signalling through the tyrosine kinase Syk. Direct binding of fibrinogen to human GPVI was shown by surface plasmon resonance and by increased adhesion of human GPVI-transfected Rbl-2H3 cells to fibrinogen relative to mock-transfected cells. Blockade of human GPVI with Fab 9O12 impairs platelet aggregation on preformed platelet aggregates in flowing blood independent of collagen and fibrin exposure. These results demonstrate that human GPVI binds to immobilized fibrinogen and show that this contributes to platelet spreading and platelet aggregation under flow.