A malignant form of non-cardiogenic pulmonary edema (NCPE) that develops soon after the termination of cardiopulmonary bypass support during cardiac surgery is rarely encountered. It sometimes requires immediate management, including venovenous extracorporeal membrane oxygenation (VV-ECMO). In the first case, a 78-year-old female patient experienced fulminating NCPE after mitral valve plasty, which caused severe respiratory failure and hemodynamic instability due to a huge amount of sputum. In the second case, a 47-year-old male patient presented with right-sided unilateral pulmonary edema with a substantial amount of sputum after minimally invasive cardiac surgery for mitral valve repair. In both cases, VV-ECMO and aggressive fluid replacement were promptly initiated. The NCPE resolved on post-operative day 2, resulting in the successful termination of VV-ECMO. NCPE leads to lethal respiratory failure with multifactorial causes during cardiac surgery. However, as NCPE is potentially transient, immediate treatment comprising VV-ECMO and aggressive fluid replacement can improve clinical outcomes.