Thrombotic deposition plays a critical role in the evolution of various vascular pathologies and is a major consideration in the development of cardiovascular devices. Although experimental evidence has shown that shear gradients in blood flow play a critical role in thrombogenesis, the impact of these gradients has not been included in previous computational models of thrombosis. The goal of the present work is to develop a predictive computational model of platelet plug formation that accounts for the role of shear gradients. A 2D computational model of platelet-mediated thrombogenesis was developed using the commercial finite element solver COMSOL Multiphysics 5.6. The model includes platelet transport, activation, adhesion and aggregation induced by both biochemical and mechanical factors. Platelet and agonist transport are described by a coupled set of convection-diffusion–reaction equations. Platelet adhesion and aggregation at the vascular surface are modeled via flux boundary conditions. Thrombus growth and its impact on blood flow are modeled using a moving surface mesh. The model provides the spatiotemporal evolution of a platelet plug in the flow field. After validation against experimental data in the literature, the model was used to predict the location and growth dynamics of platelet plugs in various vascular geometries. The results confirm the importance of considering both mechanical and chemical platelet aggregation and underscore the essential role that shear gradients play in platelet plug formation. The developed model represents a potentially useful tool for thrombogenesis prediction in pathological scenarios and for the optimization of endovascular device design.