BACKGROUND Hypoxia caused by an increase in right-to-left shunt has been reported in patients with patent foramen ovale treated with levels of positive end-expiratory pressures (PEEP) greater than 10 cmH2O. This phenomenon has not previously been described with non-invasive ventilation (NIV). METHODS A 23 year-old man with tetralogy of Fallot and a severe kyphoscoliosis was admitted at the hospital for chronic dyspnoea. Arterial blood gases on room air: pH 7.43, PaCO2 39 mmHg, PaO2 67 mmHg, HCO3- 25 mmol/l, SaO2 95%. Nocturnal oxymetry showed severe hypoxaemia resistant to oxygen. NIV with PEEP of 3 cm H2O was commenced. With ventilation, his oxygenation worsened. An echocardiogram performed during NIV showed an increase in the right-to-left interventricular gradient from 22 to 37 cmH2O, and of the right ventriculo-auricular gradient from 76 to 142 mmHg. Furthermore, his oxygen saturation decreased progressively from 95 to 85%. Following removal of NIV, the patient recovered in 15 minutes. CONCLUSIONS We report an increased right-to-left intracardiac shunt in a patient with tetralogy of Fallot. Compression of pulmonary vessels and cardiac cavities induced by NIV may have been enhanced by a reduction in thoracic compliance related to kyphoscoliosis. Right-to-left shunt in patients with kyphoscoliosis may be a contra-indication to NIV.