The outcome of antenatally diagnosed congenital diaphragmatic hernia (CDH) has remained poor despite aggressive therapeutic strategies. Since 1996, the authors have used a new approach including early surgery and inhaled nitric oxide (iNO). The aim of this study is to determine whether early surgery in combination with iNO improves the clinical outcome of antenatally diagnosed CDH. From 1988, 40 consecutive neonates with antenatally diagnosed CDH were admitted to the authors' hospital. Ten cases of fatal chromosomal anomalies or major cardiac anomalies were excluded from this study. From 1988 through 1995 (period 1: n = 13), delayed surgery was used in high-risk CDH. From 1996 through 2000 (period 2: n = 17), early surgery in combination with iNO was used. The severity of lung hypoplasia was evaluated using the fetal lung/thorax transverse area ratio (L/T). High-frequency oscillatory ventilation (HFOV) was used routinely during the study periods, and extracorporeal membrane oxygenation (ECMO) was used on basis of conventional entry criteria. The authors compared the clinical outcome, use of ECMO, and the L/T between the 2 periods retrospectively. Patients in the 2 periods were comparable in terms of birth weight, gestational age, and the L/T. The mean age at surgery was 3.1 +/- 4.9 days in period 1, and 0.8 +/- 1.1 days in period 2. Fewer infants in period 2 compared with period 1 were treated with ECMO (period 1, 62% v period 2, 6%; P <.01). There was significant difference in the survival rate between the 2 periods (period 1, 38% v period 2, 94%; P <.01). Our data suggest that early surgery and iNO improves the outcome and reduces the requirement of ECMO in the treatment of antenatally diagnosed CDH. Copyright 2002, Elsevier Science (USA). All rights reserved.