(1) To assess extracellular volume fraction (ECV) and regional systolic function in patients presenting with coronary chronic total occlusion (CTO) in areas without significant late gadolinium enhancement (LGE), and (2) to investigate the correlation between angiography collateral flow and ECV in territories supplied by CTO vessels. A total of 50 angiographically documented CTO patients and 15 age- and sex-matched normal controls were recruited to the study. Myocardial ECV, was calculated in infarcted, global non-infarcted and the entire myocardium respectively. Segmental ECV was calculated from myocardial segments within the perfusion territory of a CTO vessel. The global and regional systolic function was evaluated using ejection fraction and percent systolic thickening. ECVs in global myocardium and global non-infarcted myocardium were significantly elevated in comparison with that in controls (29.1 ± 4.2% and 26.6 ± 2.6% vs. 23.3 ± 2.0%, all P < 0.005). Global ECV significantly correlated with LV ejection fraction (r = -0.56, P < 0.001) and ECV inversely correlated with systolic thickening in global non-infarcted myocardium (r = -0.31, P < 0.05). The lower segmental ECV was associated with the presence of well-developed collaterals (P = 0.004), and multivariate binary logistic analysis demonstrated that mean segmental ECV and course of disease were the independent discriminator of collateral flow with overall diagnostic accuracy of 74.4%. In patients with CTO, ECV is found to be increased beyond that observed with LGE, and correlates with LV regional wall motion abnormality, which appears to reflect diffuse myocardial fibrosis. Mean segmental ECV value, combined with course of disease, may serve as good predictors of collateral flow.