The process of atherosclerotic plaque disruption has been difficult to monitor because of the lack of an animal model and the limited ability to directly visualize the plaque and overlying thrombus in vivo. Our aim was to validate in vivo magnetic resonance imaging (MRI) of the thrombus formation after pharmacological triggering of plaque disruption in the modified Constantinides animal model of plaque disruption. Atherosclerosis was induced in 9 New Zealand White male rabbits (3 kg) with aortic balloon endothelial injury followed by a high cholesterol (1%) diet for 8 weeks. After baseline (pretrigger) MRI, the rabbits underwent pharmacological triggering with Russell's viper venom and histamine, followed by another MRI 48 hours later. Contiguous cross-sectional T2-weighted fast spin echo images of the abdominal aorta were compared by histopathology. In all animals, aortic wall thickening was present on the pretrigger MRI. On MRIs performed 48 hours after triggering, a histologically confirmed intraluminal thrombus was visualized in 6 (67%) of the 9 animals. MRI data correlated with the histopathology regarding aortic wall thickness (R=0.77, P<0.0005), thrombus size (R=0.82, P<0.0001), thrombus length (R=0.86, P<0.005), and anatomic location (R=0.98, P<0.0001). In vivo, MRI reliably determines the presence, location, and size of the thrombus in this animal model of atherosclerosis and plaque disruption. The combination of in vivo MRI and the modified Constantinides animal model could be an important research tool for our understanding of the pathogenesis of acute coronary syndromes.