The purpose of this study was to establish an MRI protocol on a clinical scanner for assessment of left (LV) and right (RV) ventricular myocardial function of the murine heart, and to apply this protocol for the first in vivo assessment of myocardial function in a mouse model of cardiomyopathy (Desmin-/-). MRI was performed on a clinical 3 T whole body MRI system using a dedicated solenoid receive-only coil. Contiguous short axis slices were acquired covering the entire heart using a spoiled cine gradient echo sequence (TR 9-12 ms, TE 3-4 ms, α 25°, 1.0 × 0.23 × 0.23 mm³). Global LV- and RV-myocardial functional parameters such as end-diastolic ventricular volume, ejection fraction (EF), LV mass and cardiac output (CO) of Desmin-/- mice and age-matched controls were determined. Global myocardial functional data of healthy controls (n = 4) were in very good agreement with previously reported data. The transgenic mice (n = 8) revealed a significantly reduced LV- and RV-EF as well as CO. Body weight-normalized LV- and RV-end-diastolic volumes and LV mass were significantly increased. In addition desmin deficient mice exhibited segmental wall thinning and akinesia, suggesting myocardial necrosis. This study demonstrates that clinical 3 T MRI-systems may reliably be used for non-invasive assessment of LV- and RV-myocardial function in normal and in genetically engineered mice with cardiomyopathies. In addition, this proof of principle study presents first in vivo MRI data of the cardiac phenotype of desmin knock-out mice.