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Profoundly impaired left ventricular (LV) function in patients undergoing femoral veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) can result in intra-cardiac stasis and thrombus formation. There have been several attempts to improve LV unloading in patients with peripheral VA-ECMO, either by improving contractility or by venting the LV.Data from all patients who underwent femoral VA-ECMO between 2007 and 2015 due to cardiogenic decompensation were retrospectively analysed regarding intra-cardiac thrombus formation.In total, 11 of 281 patients (3.91%) with femoral VA-ECMO developed an intra- or extra-cardiac thrombus despite adequate anticoagulation therapy. None of the patients survived this serious complication.Management strategies for patients with femoral VA-ECMO support and severely impaired LV function must be reassessed to avoid insufficient LV unloading at an early stage of ECMO therapy. Early LV decompression should be considered in patients with insufficient unloading of the LV to prevent intra-cardiac thrombus formation.