The aim of the present study was to characterize coronary plaques by Multi-Slice Computed Tomography (Siemens sensation 16, Forcheim, Germany) before significant angiographic progression occurred and to compare them to non-progressing lesions. The MSCT-morphology of coronary plaques leading to a rapid angiographic disease progression is not yet studied. In a series of 68 patients who were scheduled for surveillance angiography 6 months later, MSCT-angiography was done shortly after the baseline catheterisation-procedure. After surveillance angiography rapid progressive lesions with an increase of the stenosis severity of >20% were identified and analysed on the baseline MSCT-scan and were compared to non-progressing lesions. Six months after coronary stenting we observed significant progression of de novo stenoses in 10/438 coronary segments. The progression of four lesions lead to angina pectoris symptoms and the remaining six lesions progressed silently. Analysis of the lesion morphology by MSCT revealed that 5/10 (50%) progressing lesions were non-calcified 3/10 (30%) were predominantly non-calcified and 2/10 (20%) were mainly calcified on the baseline MSCT-scan. In the 428 segments without disease progression atherosclerotic lesions were found in 225 segments on MSCT. Non-calcified plaques were identified in 46 (20%), predominantly non-calcified lesions in 58 (26%) and predominantly calcified lesions in 121 (54%) segments. The average number of diseased coronary segments between patients with and without lesion progression was not significantly different between progressors and non-progressors with a higher prevalence of non-calcified segments in the progressor group (1.1 vs. 0.63). Rapid progression of the angiographic stenosis severity during a 6 months period occurs most frequently in coronary segments revealing non-calcified or predominantly non-calcified plaques as determined by MSCT, whereas lesion progression is rare in predominantly calcified segments. This represents first evidence that non-calcified lesions may be involved in the process of plaque rupture.