Patients with angiographically normal coronary arteries sometimes exhibit delayed clearance of contrast medium. This contrast layering (CL) was tested with intravascular ultrasound (IVUS) and markers of endothelial dysfunction and oxidative stress. The study group (n = 26) consisted of patients with CL and the control group (n = 32) comprised patients with normal coronary arteries despite angina symptoms. The CL was observed in 36 coronary arteries of 26 patients in the study group. Total antioxidant status and nitric oxide levels were significantly lower; total oxidant status, malondialdehyde plasma levels, and oxidative stress index were significantly higher in patients with CL than in controls. The IVUS studies revealed that atherosclerotic plaque burden, fibrous tissue, dense calcific tissue, and necrotic core ratios were significantly higher in the coronary segments with CL compared with adjacent normal segments. These results support the concept of CL as a new angiographic appearance of early atherosclerosis.