Right-sided diaphragmatic defects represent less than 20% of all congenital diaphragmatic hernias (CDH). Recent data suggest that right CDH (R-CDH) may carry a disproportionately high morbidity as well as increased rates of extracorporeal support when compared with left CDH. Treatment of infants with R-CDH may be further complicated by anatomical distortion unique to right-sided defects. We report 2 cases of azygous vein cannulation in neonates with large isolated R-CDH. Both infants had postnatal deteriorations within 48 hours, met our criteria for extracorporeal membrane oxygenation (ECMO), and underwent venoarterial cannulations through the right neck. In each case, the venous cannula passed directly into the azygous vein and failed to provide adequate ECMO support. Echocardiography confirmed both cases of azygous cannulation. In one child, the right atrium was successfully cannulated after 90 minutes of extensive cannula manipulation. This child survived a 5-day ECMO course and is alive at 22-month follow-up. In the second child, despite prolonged efforts at cannula repositioning, cannulation of the right atrium was not achieved. We did not offer central cannulation because of a rapidly deteriorating clinical course, with expiration in several hours. At autopsy, a dilated azygous vein was evident as a result of inferior vena cava compression by a malpositioned liver. The possibility of azygous vein cannulation may be increased in neonates with R-CDH and has not been previously reported. When evaluating infants with R-CDH for ECMO, clinicians must recognize the possibility of azygous cannulation and its potentially lethal consequences, and should anticipate alternative venous cannulation.