Data of virtual histology (VH) acquired by intravascular ultrasound (IVUS) on saphenous vein graft (SVG) lesions is lacking. This study sought to report the VH IVUS findings in degenerative aortocoronary SVG lesions and correlate various types of plaque compositions (fibrous, fibro-fatty, dense calcium, and necrotic core) with different clinical and lesion characteristics. Virtual histology IVUS was performed on SVG in 38 symptomatic patients with a history of coronary artery bypass grafting, who underwent percutaneous coronary intervention on either native vessels or SVG. Measurements were made at the image slice with the smallest lumen. A total of 54 SVG lesions were analyzed; the mean graft age was 13.7 +/- 4.0 years. The mean vessel size was 5.0 +/- 1.0 mm; plaque area was 13.4 +/- 7.3 mm(2), and plaque burden was 63.0% +/- 15.0%. Fibrous tissue represented the major plaque component (62.1% +/- 17.1%). Lesions with a plaque burden of >or=70% were associated with positive remodeling, larger vessel size, higher percentage of fibro-fatty tissue, but lower percentage of dense calcium. Plaque burden was found to be positively correlated with remodeling index (r = 0.37, P = 0.01) and % fibro-fatty tissue (r = 0.49, P < 0.001) but negatively correlated with % dense calcium (r= -0.31, P = 0.03). The severity of SVG atherosclerosis paralleled with a proportional increase in fibro-fatty tissue. Unstable plaques in SVG were associated with positive remodeling, lipid-rich atheroma, and less calcium deposition, similar to the VH IVUS findings in native coronary arteries.