Hepatic artery thrombosis (HAT) is the most serious vascular complication after liver transplantation. Multiple risk factors have been identified to impact its development. Changes in haemostasis associated with end stage liver disease and the disturbance of the coagulation and anticoagulation cascades play an important role in development of this lethal complication. Early recognition and therapeutic intervention is mandatory to avoid its consequences. Pharmacological prophylaxis, by the use of antiplatelet or anticoagulant agents, is an important tool to reduce its incidence and prevent graft loss. Only a few studies have shown a clear benefit of antiplatelet agents in reducing HAT occurrence, however, these studies are limited by being retrospective and by inhomogeneous populations. The use of anticoagulants such as heparin is associated with an improvement in the outcomes mainly when used for a high-risk patients like living related liver recipients. The major concern when using these agents is the tendency to increase bleeding complications in a setting of already unstable haemostasis. Hence, monitoring of their administration and careful selection of patients to be treated are of great importance. Well-designed clinical studies are still needed to further explore their effects and to formulate proper protocols that can be implemented safely.