Serial cardiac magnetic resonance (CMR) evaluation of a highly translatable large-animal (pig) model of anthracycline-induced cardiotoxicity (AIC) shows that cumulative exposure to anthracyclines results in significantly reduced left ventricular ejection fraction and extensive mitochondrial fragmentation. Remote Ischemic Conditioning applied before each anthracycline cycle preserved cardiac contractility and left ventricular ejection fraction in long-term CMR exams. Remote Ischemic Conditioning applied before each anthracycline injection prevented doxorubicin-induced irreversible mitochondrial fragmentation and dysregulated autophagy. Remote Ischemic Conditioning is as an attractive strategy for testing in clinical trials in cancer patients at risk for developing anthracycline-induced heart failure.