This study investigated whether free-breathing T1-acquisition with the proposed region-based (RB) method is feasible to quantify ECV as an index of diffuse myocardial fibrosis. Thirty-eight patients with non-ischemic cardiomyopathy (NICM) and 20 healthy controls were examined using both breath-hold and free-breathing myocardial T1-acquisitions. ECV was measured from free-breathing images by the RB method, which was compared with the measurement on the standard pixel-wise T1-mapping. Intraclass correlation coefficient of the two methods was 0.915. Patients with NICM showed significantly higher ECV than controls for both methods. Our results suggest that free-breathing T1-acquisition with the RB method is feasible to quantify diffuse myocardial fibrosis, and is comparable to the measurement using the standard T1-mapping.