Intravascular ultrasound is an adjunct for the diagnosis of atherosclerotic peripheral vessels. In this in-vitro study, 69 segments of human peripheral arteries were fixed in formalin, examined with intravascular ultrasound and pathomorphologically evaluated. Sensitivity, specificity, both positive and negative predictive value and accuracy of intravascular ultrasound for the detection of irregular lumen contours, intraarterial structures and intimal thickening were determined for each of four quadrants. Sonographic features (echogeneity, homogeneity, shadowing of echoes) were compared to the architecture of lesions. Intravascular ultrasound detected regular (normal) lumen contours with high specificity (96.5%), a sensitivity of 65.0%, and an accuracy of 88.4%; intraluminal structures were detected with a sensitivity of 88.6%, a specificity of 97.8%, and an accuracy of 96.4%. Most atherosclerotic lesions could be localized with a sensitivity of 86.1%, a specificity of 99.1%, and an accuracy of 86.9%. Slight intimal thickening was detectable with a sensitivity of 85.9%, a specificity of 87.8%, and an accuracy of 86.2%. Comparison of sonographic features and the pathomorphological architecture of atherosclerotic lesions revealed that fibrous, atheromatous, and complex lesions without calcification did not show shadowing of echoes. The majority of fibrous or atheromatous lesions presented with homogeneous echoes; these lesions showed hypo-, hyper- and normodense echoes. The homogeneity of echoes did not help to identify the different components of combined atherosclerotic lesions. Thus, intravascular ultrasound is able to detect irregular lumen contours, intraluminal structures, and intimal thickening, but further sonographic criteria are needed to identify the architectural structure of combined lesions.