Patients with severe respiratory failure undergoing conventional mechanical ventilation typically are exposed to levels of ventilator support that place the patient at risk of barotrauma or oxygen toxicity. In severe cases, gas exchange may be inadequate despite maximal ventilator support. We report two cases of advanced respiratory failure in which augmentation of gas exchange was provided for prolonged periods (18 and 13 days) with an intravenacaval hollow-fiber membrane oxygenator (IVOX). Following implantation, significant reductions in ventilator support were possible with improvement in arterial blood gas values. No significant complications were noted. IVOX can provide clinically useful augmentation of gas exchange in respiratory failure and can be used for prolonged periods.