Coronary angioscopy (CA) provides direct visualization of the endoluminal surface of coronary vessels. The usefulness of CA during coronary angioplasty of angiographically complex lesions remains to be established. This study was designed to determine the value of CA to elucidate the underlying substrate of angiographically complex lesions. Forty-seven consecutive patients with angiographically complex lesions were studied with CA before coronary intervention. Mean age of the group was 59 ± 9 years; six patients were women. Forty (85%) patients had unstable angina. Complex angiographic lesions included coronary occlusions ( n = 23) (14 with Thrombolysis in Myocardial Infarction coronary flow grade 0 and nine with flow grade 1), lesions with intraluminal filling defects suggestive of thrombus or ulceration ( n = 8), and lesions that were highly eccentric ( n = 16). Items analyzed with CA included red thrombus (lining or protruding) and plaque color (yellow, white, or mixed). In all patients, CA visualized the protruding material causing the angiographic appearance. At this site CA detected red thrombus in 34 (72%) patients (14 protruding, 20 lining) and atherosclerotic plaque in 45 (96%) patients. At the site of the angiographically complex lesion, plaque was classified as predominantly yellow in 24 patients, mixed in 12, and white in nine. The incidence of thrombus on CA was higher for occluded vessels (91%) or lesions with intraluminal filling defects or ulceration (87%) than in eccentric lesions (37%) ( p < 0.05). However, plaque coloration was not significantly different among these three angiographic subgroups. Initial procedural success (without stent requirement) was lower in lesions showing protruding thrombus on CA (64% vs 91%, p < 0.05). Thus most angiographically complex lesions contain thrombus. On CA red thrombus was more frequently identified on occluded vessels and lesions with filling defects or ulceration than in eccentric lesions. Yellow or mixed plaques are common in these patients, suggesting lipid-laden plaques as the underlying pathologic substrate of angiographically complex lesions. (Am Heart J 1997;134:703-11.)