Stroke is a leading cause of morbidity and mortality and the most common cause of neurological disability in older individuals. Prevention of recurrent stroke includes risk factor modification as well as the use of therapies that inhibit platelet activation. One such recommended therapy, dipyridamole, is given in combination with aspirin. Dipyridamole's inhibitory effect is thought to be due to inhibition of the adenosine transporter leading to an increase in cAMP, an inhibitor of platelet aggregation. However, recent studies suggest that dipyridamole possesses beneficial properties in vasculature in addition to anti-platelet effects. This includes direct and indirect effects on the endothelium such as inhibition of proliferation, antioxidant, and anti-inflammatory properties as well as their subsequent effect on cell signaling. The purpose of this review is to examine whether the recently identified beneficial antioxidant and anti-inflammatory properties of aspirin/extended-release dipyridamole may partially underlie the clinical benefits observed in the secondary prevention of stroke.