Transcranial Doppler (TCD) is able to detect cerebral hemodynamic changes in real-time. Impairment of cerebral blood flow during veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) treatment is referred to in the literature. Several cerebrovascular complications can affect VA ECMO patients, eventually leading to brain death (BD). Transcranial Doppler is a worldwide accepted technique for cerebral circulatory arrest (CCA) diagnosis for BD confirmation, and in Italy, it is mandatory in certain clinical conditions. Nowadays, no data have been published on the use of TCD as a confirmation test in VA ECMO patients evolved to BD. The aim of our study was to investigate the feasibility of TCD in CCA diagnosis during VA ECMO treatment. Thirty-two TCD examinations, performed in 25 patients on VA ECMO, were retrospectively analyzed, and factors that could be responsible for TCD waveforms abnormalities were reviewed. Differences in TCD patterns were detected depending on values of left ventricular ejection fraction and the absence or presence of intraaortic balloon pump (IABP). Four categories of different TCD patterns were then identified. In five BD patients, diagnostic CCA patterns in all cerebral arteries were identified by TCD. Our data suggest that cerebral hemodynamic changes due to both residual cardiac function and the effects of IABP can be detected by TCD in VA ECMO patients. In the case of BD, TCD seems to be a reliable instrumental test for CCA diagnosis in patients on VA ECMO when a pulsatile flow is maintained (native or IABP support).