Venovenous extracorporeal membrane oxygenation (V-V ECMO) is a life-saving organ support for patients with severe respiratory failure. One of the possible complications involves cannula positioning, but the literature has largely focused on recirculation. We report five cases, from a cohort of 320 patients treated at a high-volume ECMO center, in which the tip of the long, non-multiperforated return cannula in a femoro-femoral V-V ECMO configuration inadvertently crossed the interatrial septum. This resulted in a veno-left atrial (V-LA) configuration with a massive right-to-left shunt of hyperoxygenated blood. The malposition was not clinically evident during the ECMO run and only became apparent during weaning attempts, when abrupt desaturation occurred. In retrospect, all patients exhibited strikingly high arterial partial pressure of oxygen (PaO₂) levels, absent recirculation, low sweep gas requirements, and excellent exercise tolerance—features that may help raise clinical suspicion. All cases were ultimately resolved by cannula repositioning, and no interatrial defect was identified in follow-up among the four survivors. Inadvertent V-LA ECMO is a rare but underrecognized complication. Early recognition is essential to avoid misinterpreting this phenomenon as treatment failure during weaning. Although it carries potential risks, such as systemic embolism or left atrial overload, it may also confer physiological benefits in selected clinical scenarios.