In this issue of Blood, Chung and colleagues demonstrate in vitro and in an animal model that von Willebrand factor (VWF) self-association under shear stress can be modulated by the high-density lipoprotein and apolipoprotein A-I (HDL/ApoA-I) complex, with significant reduction in the length and thickness of VWF fibers. These antiadhesive and antithrombotic properties of HDL/ApoA-I may connect the pathology of microvasculature with that of large vessels (atherosclerosis with arterial thrombosis) and might suggest novel approaches to these thrombotic disorders.