The recognition that stroke and other ischemic events are manifestations of chronic progressive inflammation has had a great impact on the development of prevention strategies. The most recent American Heart Association guidelines recommend combination aspirin and extended-release dipyridamole over aspirin alone for patients with prior ischemic stroke or transient ischemic attack. Although aspirin and extended-release dipyridamole have long been recognized for their antiplatelet activities, there is now evidence that these drugs also have complementary antiinflammatory properties that contribute to improved outcomes when used to prevent secondary stroke. In the Second European Stroke Prevention Study (ESPS-2), the addition of extended-release dipyridamole to low-dose aspirin significantly reduced the risk of recurrent ischemic stroke without significantly increasing bleeding. Also, in the recent European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT), a combination of aspirin and extended-release dipyridamole was superior to aspirin alone for reducing the occurrence of the primary combined end point of vascular death, nonfatal stroke, nonfatal myocardial infarction, and major bleeding complications. The added benefit without worsening bleeding may be attributable, in part, to the antiinflammatory actions of this combination therapy.