Background Extracorporeal membrane oxygenation (ECMO) is an effective extracorporeal life support technology that has been applied to treat cardiorespiratory failure patients. Some medical centers have started using ECMO on awake, non-intubated, spontaneously breathing patients, as this strategy offers several benefits over mechanical ventilation. However, most awake-ECMO methods focus on venovenous ECMO, and few cases of awake veno-arterial ECMO (V-A ECMO) have been reported, especially in perioperative acute heart failure. Therefore, our study aimed to examine awake—V-A ECMO cases that were not given continuous sedation or invasive mechanical ventilation (IMV) during perioperative heart failure. Method In total, 40 ECMO patients from December 2013 to November 2019 were divided into 2 groups (the awake-ECMO group and the asleep-ECMO group) according to the ventilation use. The demographics, patient outcomes, and ECMO parameters were collected and retrospectively analyzed. Results We identified 12 cases of awake ECMO without continuous ventilation, and 28 cases of simultaneous IMV and ECMO (asleep ECMO). Awake-ECMO patients showed fewer complications and better outcomes compared to ventilation patients. All patients in the awake group were successfully weaned off ECMO, while only 5 (18%) patients were weaned off ECMO in the asleep group. Furthermore, 9 (75%) patients survived until discharge in the awake group vs. 3 (11%) in the asleep group; 3 patients died of septic shock after weaning in the awake group, while 25 patients died of septic shock, hemodynamic disorder, bleeding, cerebral hemorrhage, etc., in the asleep group. These complications, including bleeding, pneumonia, hemolysis, and abdominal distension, etc., occurred less frequently in the asleep group compared to the awake group (P<0.05). Conclusions Awake V-A ECMO is an effective, feasible, and safe strategy in patients with perioperatively acute heart failure and can be applied as a bridge to cardiac function recovery or transplantation.