Background: In vivo identification of plaque composition may allow the detection of vulnerable plaque. While the identification of calcified coronary plaque using multi-detector computed tomography (MDCT) is relatively easy due to its significantly higher CT attenuation, differentiation of non-calcified plaques remains challenging because of their small differences in CT attenuation. We compared 64-slice MDCT with virtual histology (spectral analysis of IVUS backscatter signals; VH) to investigate the potential of 64-slice MDCT to differentiate composition of non-calcified plaque. Methods: Fifty-five consecutive patients (stable/unstable angina: 34/21; mean age 62.4짹18.4 years) were enrolled. The mean CT density (measured as Hounsfield unit; HU) of non-calcified coronary plaque was compared with relative percentage of each plaque components (fibrous, fibro-fatty, dense calcium and necrotic core) analyzed by VH. Results: The mean heart rate during the MDCT scan was 58짹6 /min. Comparison between 64-slice MDCT and VH was available in 83 coronary plaques. Overall relative percentage of fibrous, fibro-fatty, dense calcium and necrotic core area were 68.4짹9.8%, 19.4짹7.6%, 0.99짹0.1%, and 11.2짹3.4% respectively. There were a significant negative correlation between mean CT density and relative percentage of lipid core area (r=0.61; p<0.001) and a positive correlation between mean CT density and relative percentage of fibrotic tissue area (r=0.63; p<0.001). However relative area of fibro-fatty tissue and dense calcium were not significantly correlated with CT density (r=0.56, p=0.08; r=0.08, p=0.56). CT density of the plaque with less than 10% relative lipid core area was significantly lower than either with 10~40% or with more than 40% (77.6짹42.3HU vs. 49.3짹27.2HU vs. 45.5짹35.5HU; p=0.03). However CT density between the plaque with 10~40% relative lipid core area and with more than 40% was not significantly different (p=0.43). Conclusion: 64-slice MDCT may play an important role in differentiating plaque compositions, even though there was substantial overlapping in CT attenuation values between non-calcified plaques.