Independent lung ventilation (ILV) is recognized as a method of treating unilateral lung disease. We report the use of ILV in a 22-year-old woman with acute respiratory failure and complex congenital heart disease with different sources of left and right pulmonary blood flow. She had a palliated single-ventricle circulation with pulsatile pulmonary blood flow from an aorto-pulmonary central shunt to her left lung and nonpulsatile pulmonary blood flow via a classic Glenn shunt (superior vena cava to right pulmonary artery). On admission she was hypoxemic and hypotensive. Her chest radiograph revealed opacification of the left lung and hyperinflation of the right lung, which was more compliant than the left lung. Following placement of a double-lumen endotracheal tube, synchronized ILV was instituted. ILV allowed us to deliver lower ventilator pressure to the right lung, which alleviated the over-distention of the right lung (to which pulmonary blood flow was supplied by the nonpulsatile Glenn shunt) while higher airway pressures were delivered to the diseased left lung, to facilitate re-expansion. There was immediate improvement in gas exchange and blood pressure. After 3 days the double-lumen endotracheal tube was changed to a single-lumen tube. She was extubated on day 6 and discharged on day 13. This case demonstrates the advantage of ILV in a patient with abnormal pulmonary blood flow and different lung mechanics in the left and right lungs.