Cardiovascular devices such as vascular grafts, stents, and heart valves have been widely used to treat cardiovascular diseases. The failure of these devices is usually initiated by the formation of thrombus and neointima on the device surfaces. Antithrombogenic surface modifications have been employed to improve the performance of these devices. In addition to biochemical modifications, tissue engineering approaches hold the promise to fabricate nonthrombogenic biological substitutes for cardiovascular tissues and devices. Endothelial cells (ECs) and stem cells have been used to cover blood-contacting surfaces. Furthermore, for tissue-engineered vascularized tissues and organs, a nonthrombogenic vascular network is essential for mass transfer and the integration of functional tissues and organs into the host upon transplantation. This review discusses the advances in antithrombogenic approaches for surface modifications and cardiovascular tissue engineering.