Massive pulmonary embolism poses a therapeutic challenge, especially when thrombolytics are controversial. We describe the complicated course of an exceptional case of massive pulmonary embolism exhibiting paradoxic embolization with a thrombus lodged in the foramen ovale. Thrombolysis was considered contraindicated and surgical intervention was performed. Postoperatively, persistent pulmonary hypertension and impending right ventricular (RV) failure necessitated the initiation of extracorporeal life support (ELS), accompanied by therapeutic heparinization, inhaled nitric oxide, levosimendan and sildenafil. On day 8, the patient was successfully weaned from ELS with excellent neurological recovery and virtual normalization of RV pressures and dimensions. (Contra-) indications for thrombolysis and surgical embolectomy are reviewed. The intriguing role of ELS in conjunction with therapeutic heparinization and pharmacological unloading of the right-sided vasculature and the RV is discussed.