The association between acquired aplastic anemia (AA) and hepatitis/acute liver failure has been well characterized as AA temporally after the presentation of acute hepatitis. In this case series we report 2 cases of patients who present with AA occurring simultaneously with the development of acute liver failure. This is among only a few reported cases known to date in which AA occurs simultaneously with impending liver failure. More importantly, this is the first report that demonstrates the feasibility of administering immunosuppressive therapy before complete resolution of the hepatic dysfunction and with excellent results. Both of our cases avoided orthotopic liver transplantation through the use of timely immunosuppressive therapy, demonstrating the potential role of medical management to avoid transplantation in these patients. Previous studies have suggested a link between an unidentified viral process and immune dysregulation that may lead to the development of AA after acute hepatitis. These 2 cases support the rationale that in our patients the 2 disease processes may share a common etiology and encourage further research into the complex pathogenic mechanism affecting these 2 different organ systems at varying points in time.