One of the main features of liver fibrosis is the expansion of the interstitial space. All water-soluble CT contrast agents remain confined in the vascular and interstitial space constituting the fractional extracellular space (fECS). Indirect measure of its expansion can be quantified during equilibrium phase with CT. The goal of this prospective study was to assess the feasibility of dual-energy CT (DECT) with iodine quantification at equilibrium phase in the evaluation of significant fibrosis or cirrhosis. Thirty-eight cirrhotic patients (according to Child-Pugh and MELD scores), scheduled for liver CT, were enrolled in the study group. Twenty-four patients undergoing CT urography with a 10-min excretory phase were included in the control group. fECS was calculated as the ratio of the iodine concentration of liver parenchyma to that of the aorta, multiplied by 1 minus hematocrit. Final study and control group were, respectively, composed of 22 and 20 patients. Mean hepatic fECS value was statistically greater in study group (P < 0.05). Positive correlation was observed between hepatic fECS value and MELD score (r = 0.64, P < 0.05). Analysis of variance showed statistical differences between control group and the Child-Pugh grades and between Child-Pugh A and B patients and Child-Pugh C patients (P < 0.05). ROC curves analysis yielded an optimum fECS cutoff value of 26.3% for differentiation of control group and cirrhotic patients (AUC 0.88; 86% sensitivity, 85% specificity). Dual-source DECT is a feasible, noninvasive method for the assessment of significant liver fibrosis or cirrhosis.