Atherosclerotic plaque rupture and erosions precipitate thrombus formation and may lead to an acute ischemic syndrome. Lipids and lipoproteins modulate the expression and/or function of thrombotic, fibrinolytic and rheologic factors, and thereby influence hemostasis and potential tissue damage resulting from vascular injury. Triglyceride-enriched lipoproteins are accompanied by elevations in factor VII clotting activity, plasminogen activator inhibitor (PAI-1) and viscosity of blood and plasma. Low density lipoprotein (LDL) promotes platelet activation and tissue factor expression and LDL levels correlate with levels of vitamin K dependent coagulation factors and fibrinogen. Conversely, LDL inhibits tissue factor pathway inhibitor (TFPI) which limits activation of the extrinsic coagulation pathway. High density lipoprotein (HDL) has anti-atherothrombotic properties that result from inhibition of platelet and erythrocyte aggregation, reduced blood viscosity and suppression of tissue factor activity and PAI-1 activity and antigen levels. The effects of lipids and lipoproteins on hemostasis and rheology may have important implications for the clinical sequelae following plaque disruption and erosion.