Mitoxantrone is an immunosuppressive drug usually delivered in severe relapsing remitting multiple sclerosis. It can also be used in secondary progressive and progressive relapsing remitting multiple sclerosis. Left ventricular ejection fraction has to be monitored because of the cardiotoxicity risk of mitoxantrone. Acute cardiac side effects in multiple sclerosis have not yet been described. We report the single case of an acute heart failure occurring in a cohort of more than 800 patients treated with mitoxantrone. We discuss about interruption criteria as maximal cumulative dose allowed and left ventricular ejection fraction cut off value.