Plasma levels of von Willebrand factor (VWF) are increased in patients with cardiovascular risk factors. Various studies aimed to elucidate the relation of VWF with thromboembolic cardiovascular events, ischaemic stroke as well as with peripheral arterial occlusive disease. In the general population, there is only a weak association between VWF levels and future cardiovascular events or stroke. In contrast, VWF levels are predictive in patients with documented vascular disease. Those patients with increased VWF suffer a higher incidence of major adverse cardiac events including death. The extent of the VWF release and its levels independently predict clinical outcome in patients with acute coronary syndromes. Elevated VWF levels have also been observed in patients with atrial fibrillation compared to controls and predict outcome. This may at least in part be attributable to the association of VWF with underlying cardiovascular risk factors. Hence, VWF correlates with Framingham and CHADS stroke risk stratification score and can be used as a marker in patients with AF. However, VWF is not only a predictor; it also plays a crucial role in thrombogenesis. This fact has made VWF a promising target for research into new antiplatelet therapies that specifically inhibit VWF. This review focuses on the role of VWF in ACS, ischaemic stroke and peripheral arterial disease and the relevance of therapeutic interventions targeting VWF for ACS patients.