Negative pressure ventilation (NPV) has been used to assist patients with respiratory failure. Venovenous extracorporeal membrane oxygenation (V-V ECMO) supports patients with acute lung injury who do not respond to conventional therapy. Some patients remain on prolonged ECMO support without access to lung transplantation. We report a 40-year-old woman cannulated for V-V ECMO due to refractory hypoxemia (PaO₂/FiO₂ of 58) on hospital day 20 for ARDS from bacteremia and native mitral valve endocarditis. After 108 days, she continued to require ventilator and ECMO support. Applying a negative-pressure Cuirass device in combination with positive pressure ventilation (PPV) improved her carbon dioxide clearance, enhanced overall ventilation/perfusion matching, and facilitated decannulation. Using NPV to assist in V-V ECMO weaning is a novel application of a legacy technology. This case shows NPV as an effective adjunct to PPV for patients on prolonged ECMO support with no other options.