Fulminant myocarditis (FM) has unacceptable high mortality. This study aimed to evaluate the therapeutic efficacy of a life support-based comprehensive treatment regimen (LSBCTR), a completely novel treatment regimen, for FM. A total of 169 FM patients recruited from January 2008 to December 2018 were divided into two groups: patients receiving LSBCTR (81 cases), which includes (i) mechanical life support (positive pressure respiration, intra-aortic balloon pump with or without extracorporeal membrane oxygenation), (ii) immunomodulation therapy using sufficient doses of glucocorticoids and immunoglobulins, and (iii) application of neuraminidase inhibitors, and those receiving conventional treatment (88 cases). The endpoints were in-hospital death and heart-transplantation. Of all the population, 44 patients (26.0%) died in hospitals. In-hospital mortality was 3.7% (3/81) for LSBCTR group and 46.6% (41/88) for traditional treatment (P<0.001). Early application of LSBCTR, mechanical life support, neuraminidase inhibitors, and immunomodulation therapy significantly contributed to reduction in in-hospital mortality. This study describes a novel treatment regimen for FM patients that dramatically reduces in-hospital mortality. Its generalization and clinical application will efficiently save lives although further optimization is needed. This study offers an insight that virus infection induced inflammatory waterfall results in cardiac injury and cardiogenic shock and is the therapeutic target.