Postpneumonectomy syndrome involves mediastinal shift causing dynamic airway obstruction via compression of the main bronchus and distal trachea. A few case reports describe the development of ARDS in patients with postpneumonectomy syndrome. Reeb et al. (2017) describe the mortality of postpneumonectomy ARDS anywhere from 33% to 88%. One may encounter difficulty in intubation and ventilation as parameters based on ideal body weight may not apply. Prone positioning ventilation and ECMO have been successfully used in isolated cases. We present such a case and highlight challenges in management. A 70-year-old male Vietnam veteran with remote history of right pneumonectomy thirty years prior presented with fever, cough, and dyspnea. Physical exam was significant for T 36.3°C, BP 162/73, heart rate 145 BPM, RR 22 breaths/minute, ht. 1.72 m, and wt. 78 kg, with transmitted right lung sounds and rhonchi on the left. Labs showed WBC 23.92/nL and procalcitonin 0.84 ng/mL. CXR showed left infiltrate and opacification of right hemithorax with right mediastinal shift. EKG showed atrial fibrillation. He was started on broad spectrum antibiotics for pneumonia, but deteriorated, and was intubated for respiratory distress from ARDS. Vasopressors were initiated for shock. Given the history of pneumonectomy, he was initially ventilated with lower tidal volumes (320 mL). However, incremental changes were made to tidal volumes, and ETT was repositioned several times for hypoxia. Epoprostenol and cisatracurium were also initiated. Positional changes would lead to sudden desaturation; hence, prone positioning ventilation was not done. He was not considered for ECMO due to his pneumonectomy status. Unfortunately, his condition worsened progressively and he expired. The guidelines for ARDS are well established. However, postpneumonectomy patients are unique as seen in our patient. It is unclear whether an endobronchial tube advanced into the left bronchus could have helped difficult airway management resulting from suspected postpneumonectomy syndrome as suggested by CXR. Higher tidal volumes were also unsuccessful in alleviating hypoxia and led to persistently elevated plateau pressures and driving pressures as high as 23, which was inconsistent with our goal of lung protective ventilation. Few case reports describe the successful use of prone positioning ventilation or ECMO in postpneumonectomy patients with ARDS. Although not well studied, low tidal volumes supported with ECMO may have been a favorable strategy for our patient.