Background Angiographic assessment of left main coronary artery (LMCA) stenosis is often difficult and unreliable. To date, intravascular ultrasound (IVUS) is used to determine the significance of lesions in patients with LMCA stenosis of uncertain significance. We aimed to prospectively show the ability of multidetector computed tomography (MDCT) to assess LMCA luminal and plaque dimensions, and to characterize atherosclerotic plaque, as compared to IVUS and quantitative coronary angiography (QCA), in patients with angiographically uncertain LMCA stenosis. Methods Twenty patients, with angiographically uncertain LMCA stenosis, underwent coronary evaluation with IVUS, QCA and 16-slice MDCT. Minimal lumen diameter (MLD), minimal lumen area (MLA), lumen area stenosis (LAS) and plaque burden (PB) were assessed. Results The MLD (median [interquartile range]) was 3.2 mm (2.5-3.7) by IVUS, 2.8 mm (2.3-3.3) by QCA (r = 0.52, P < 0.05), and 2.8 mm (2.5-3.8) by MDCT (r = 0.77, P < 0.01). MDCT estimated MLA as 10.7 mm(2) (7.1-12.6) Vs. 9.9 mm(2) (6.5-13.5) by IVUS (r = 0.93, P < 0.01). Very high correlations were observed between MDCT and IVUS in assessing LAS (mean +/- SD) (25.8 +/- 19.1% and 29.0 +/- 24.9% respectively, r = 0.83, P < 0.01), and PB (49.2 +/- 15.8% and 49.2 +/- 19.7% respectively, r = 0.94, P < 0.01). MDCT assigned plaque as being non-calcified with a sensitivity of 100%, while calcified plaques with a sensitivity of 75%. Conclusion A high degree of correlation was found between MDCT and IVUS regarding the assessment of minimal lumen diameter and area, lumen area stenosis and plaque burden as well as plaque characterization in patients with angiographically borderline LMCA stenosis. Therefore, in patients selected for non-invasive coronary tree evaluation, MDCT may provide a valuable tool for the assessment, decision-making and follow-up of patients with uncertain LMCA disease.