Compared with the 2009 pandemic influenza A (H1N1), the seasonal influenza A (H3N2) in 2011?2012 was self-limited and mild. However, some cases proceeded to acute respiratory distress syndrome (ARDS) due to underlying medical history. Here we report two cases with influenza A (H3N2) progressing to fatal ARDS. One case with several underlying medical conditions eventually died from multi-organ failure despite the application of extracorporeal membrane oxygenation. When patients are suspected to have influenza, it is imperative to investigate their medical histories and risk factors. If they have many co-morbidities or risk factors, clinicians should initiate aggressive management immediately regardless of the type of influenza infection.