Many stroke research groups utilize the model of middle cerebral artery occlusion induced by insertion of an intraluminal thread, owing to its pragmatism and reliability of cerebral infarct generation. However, 75% of stroke cases result from a thromboembolic event and 10% from occlusive atherothrombosis in situ. Here, we characterize a mouse model of repeated thromboembolic stroke, which closely mimics the intravascular pathophysiology of arterial thrombus generation from an atherosclerotic plaque, and subsequent release of a thrombus into the cerebral circulation as an embolus. Common carotid artery thrombosis (CCAT) was induced photochemically leading to non-occlusive platelet aggregation in C57/BL6 male mice (n=35), and was followed by mechanical assistance to facilitate release of the thrombus (MRT) and thus promote embolism. Six experimental groups, differing by changes in the surgical protocol, were used for the purpose of determining which such procedure yielded the most reliable and consistent brain infarct volumes with the lowest mortality at 3 days after surgery. The group which best satisfied these conditions was a double insult group which consisted of animals that underwent CCAT for 2 min by means of argon laser irradiation (514.5 nm) at an intensity of ca. 130 W/cm(2), with concomitant injection of erythrosin B (EB) (35 mg/kg infused over those same 2 min), followed by MRT 1 min later; the entire procedure was repeated 24h later. This group showed a percent of brain lesion volume of 15+/-4% (mean+/-S.D.) with no associated 3-day mortality. Compared to a single insult group which sustained a percent brain lesion volume of 7+/-3%, there was a statistically significant (p<0.05) increase in the volume of infarction in the double-insult group.