Background: In patients with chronic thromboembolic pulmonary hypertension (CTEPH) with high thrombus burden and severe pulmonary arterial hypertension, pulmonary endarterectomy (PEA) carries a high risk of postoperative cardiorespiratory complications requiring extracorporeal membrane oxygenation (ECMO) as a bridge to recovery. Methods/Results: We present a case of a 77 year old patient who underwent PEA after presenting with profound acute-on-chronic respiratory failure (O2 saturation of < 80% on 100% FiO2) on a background of CTEPH with severe right ventricular dysfunction. The patient had a massive thrombus burden with dilation of the right pulmonary artery requiring repeated cycles of deep hypothermic circulatory arrest to facilitate complete surgical clearance. Profound post-bypass right ventricular dysfunction and reperfusion pulmonary oedema necessitated transitioning from cardiopulmonary bypass to central venoarterial ECMO. This was followed by staged reconfiguration of the ECMO circuit, initially to femoro-atrial veno-venous (VV) ECMO after cardiac recovery, and subsequently femoro-jugular VV ECMO to facilitate chest closure. After gradual respiratory recovery, the patient was decannulated from ECMO at postoperative day nineteen and discharged to rehabilitation on day 59. At fourteen weeks postoperatively, he is functionally independent, on no supplemental oxygen with no signs of right heart failure, and with moderately impaired right ventricular function, no tricuspid regurgitation and no left sided heart pathology. Conclusions: This case illustrates the feasibility of pulmonary endarterectomy in patients with massive thrombus burden as well as the utility of tailored use of different ECMO configurations in high-risk cardiothoracic surgical patients commensurate with their pathophysiologic state as it evolves intraoperatively and postoperatively.