AbstractBackground: The aim of this study was to investigate reproducibility and accuracy of computer‐assisted coronary plaque measurements by multislice computed tomography coronary angiography (QMSCT‐CA). Methods and Results: Forty‐eight patients undergoing MSCT‐CA and coronary arteriography for symptomatic coronary artery disease and quantitative intravascular ultrasound (IVUS, QCU) were examined. Two investigators performed the QMSCT‐CA twice and a third investigator performed the QCU, all blinded for each other's results. There was no difference found for the matched region of interest (ROI) lengths (QCU 29.4 ± 13 mm vs. QMSCT‐CA 29.6 ± 13 mm, P = 0.6; total length = 1,400 mm). The comparison of volumetric measurements showed (lumen QCU 267 ± 139 mm3 vs. mean QMSCT‐CA 177 ± 91 mm3, P << 0.001; vessel 454 ± 194 mm3 vs. 398 ± 187 mm3, P << 0.001; and plaque 189 ± 93 mm3 vs. 222 ± 121 mm3; investigator 1, P = 0.02; and investigator 2, P = 0.07) significant differences. Automated lumen detection was also applied for QMSCT‐CA (218 ± 112 mm3, P << 0.001 vs. QCU). The interinvestigator variability measurements for QMSCT‐CA showed no significant differences. Conclusion: QMSCT‐CA systematically underestimates absolute coronary lumen‐ and vessel dimensions when compared with QCU. However, repeated measurements of coronary plaque by QMSCT‐CA showed no statistically significant differences, although, the outcome showed a scattered result. Automated lumen detection for QMSCT‐CA showed improved results when compared with those of human investigators. © 2007 Wiley‐Liss, Inc.