Background/Objectives: In recent decades, the advantages of minimizing surgical trauma have led to the development of minimally invasive surgical procedures. While the benefits often outweigh the risks, several challenges are encountered that are not present in conventional surgical approaches. Unilateral pulmonary edema (UPE) after mitral interventions performed through a right-sided approach is a rare but potentially life-threatening event. Methods: We present the case of a 49-year-old patient who underwent endoscopic mitral valve repair. Immediately following ICU admission, the patient’s oxygen saturation suddenly dropped, and serous discharge was exteriorized from the endotracheal tube, with a thoracic X-ray revealing right-sided unilateral pulmonary edema. Results: The therapeutical course was complex. The patient developed hemodynamic instability, leading to cardiac arrest, which required cardiopulmonary resuscitation and the initiation of peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO). The endotracheal cannula was replaced with a right-sided double-lumen cannula, and the patient was placed on two ventilators operating independently. The patient was weaned off extracorporeal membrane oxygenation (ECMO) on the fifth day and extubated on the sixth postoperative day. Conclusions: We successfully treated this patient using ECMO and independent lung ventilation. Several cases have been described in the literature, but the pathogenesis and risk factors of UPE remain unclear. Management depends on the severity of UPE, but a deeper understanding of its underlying mechanisms could provide cardiac surgeons with enhanced strategies for preventing UPE and implementing timely interventions.