This in vitro study evaluated the performance of 16-slice multidetector computed tomography (MDCT) in the assessment of carotid plaque components, with histology as the gold standard. Twenty-one specimens (n=21) were scanned and reconstructed after optimization of the protocol. Three corresponding MDCT images and histologic sections were selected from each specimen. The Hounsfield values (HV) of the major plaque components (calcifications, fibrous tissue and lipid) were assessed. Plaque areas (mm2) assessed with MDCT were compared with the results from histologic analysis. A value of 140 kVp and an intermediate reconstruction algorithm was the optimal protocol. In 15 out of 21 specimens it was possible to match MDCT images with histology. The HV of calcifications, fibrous tissue and lipid were 45+/-21, 79+/-20 and 960+/-491 HU (P<0.001), respectively. Plaque areas were compared in 27 matched levels. The calcified and lipid areas on MDCT and histology correlate well (R2=0.83 and R2=0.68, respectively). The mean difference in lipid area was 0.1 mm2 (95% CI=-2.1-2.3 mm2). This in vitro study showed that MDCT is capable of characterizing and quantifying the lipid rich portion of the atherosclerotic plaque.