Thrombotic events occurring in either arteries or veins are the primary causes of fatal perioperative cardiovascular events. Risk factors for deep vein thrombosis, several of which are evidently associated with specific surgical procedures, are quite different from those for arterial thrombosis (e.g., aging or atherosclerotic diseases). Thrombus formed in arteries consists mainly of platelets coated with fibrin (i.e., white thrombus), while venous thrombus formed at relatively lower shear stress consists of all blood components including erythrocytes as well as leukocytes infiltrated with fibrin (red thrombus). Clinical evidence indicates beneficial roles of neuraxial anesthesia/ analgesia in the prevention of VTE for patients undergoing high risk surgical procedures. To date, mechanisms of action of drugs used for neuraxial anesthesia/analgesia to prevent venous thrombosis are uncertain. However, accumulation of clinical as well as experimental findings points to the involvement of immune cells (especially monocytes) in red thrombus generation and to the interaction of anesthetics with these cells. We also suggest that adhesion molecules associated with the formation of monocyte platelet aggregates as well as substance P: neurokinin-1 receptor (SP/NK1R) pathway that involves neurogenic inflammation are crucial. Local anesthetics and NK1R antagonists are candidate drugs that may possess the capability to prevent venous thrombotic disorders in perioperative settings.