Despite improvements in prenatal diagnosis and neonatal intensive care, the Congenital Diaphragmatic Hernia (CDH) Registry still records a 64% survival rate. Many reports demonstrate, however, that approximately 80% of CDH patients with no other malformations may survive if managed with permissive hypercapnia, gentle ventilation, high-frequency oscillatory ventilation (HFOV), surfactant, inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO), and delayed surgical repair. We wished to define the evolving outcome of CDH newborns using a protocol approach to management, which includes surgery in the neonatal intensive care unit (NICU) or operating room (OR). From January 1996, data were collected prospectively on 42 consecutive live-born infants with CDH. Newborns symptomatic at birth were sedated and paralyzed in the delivery room, and treated with elective HFOV, iNO, surfactant, and ECMO as necessary, delaying surgical repair until their clinical conditions were stable. Once the CDH newborn was stabilized, a trial on conventional ventilation was started at least 24 hours before surgery; however, if the patient was unstable, therapy was switched back to HFOV and surgery was performed in the NICU. Demographic and clinical parameters were compared between CDH newborns who underwent surgery in the NICU and in the OR. The two groups were comparable in terms of clinical characteristics and baseline ventilatory and blood gas values. Mean age at surgery was 3 +/- 2 days. After surgery, the NICU group had more infectious complications. However, the survival rate of uncomplicated CDH was 78% and a low rate of chronic lung disease was reported. A prolonged phase of presurgery stabilization is proposed and strict control of infection is recommended for the CDH newborns who might benefit from an exclusive HFOV and NICU surgery.