Lesion eccentricity with irregularities on coronary angiography is associated with ruptured plaques and thrombus based on postmortem and clinical angiographic studies. However, the predictive value of such angiographic markers of plaque disruption and thrombus remains to be determined in vivo. The purpose of this study was to establish whether Ambrose's angiographic coronary lesion types and other angiographic criteria predict the presence of disrupted plaques and thrombus using intracoronary angioscopy. Angioscopy was performed before angioplasty in 60 patients with various coronary syndromes and culprit lesions that were not totally occlusive. Lesions were classified angiographically according to Ambrose's criteria as concentric, type I and II eccentric, and multiple irregularities, or as complex or noncomplex, and then compared with the corresponding angioscopic findings. Disruption and/or thrombus were seen in 17 of 19 type II eccentric lesions and 21 of 23 angiographically complex lesions and had the highest positive predictive value to detect complicated atherosclerotic plaques (type II eccentric lesions: positive predictive value 89%, 95% confidence intervals 67% to 99%; complex lesions: 91%, 95% confidence intervals 72% to 99%). We conclude that Ambrose's type II eccentric stenoses and angiographically complex lesions are strongly associated with disrupted plaques and/or thrombus as assessed by angioscopy in patients and represent unstable plaque substrates.