Abstract Objectives The objectives of the study were to provide a review of patients with giant omphalocele managed in a single institution (2001-2006), focusing on medical management in the neonatal period, and to evaluate short-term outcomes. Methods Data from 14 neonates with giant ompholocele (abdominal wall defect >5 cm and/or containing liver) and the absence of malformation and chromosomal anomalies during fetal screening were retrospectively reviewed. All were intubated and sedated before surgical treatment. Initial management consisted of progressive reduction of the herniated organs by gentle compression. After sequential reduction, abdominal wall closure was attempted at the skin and fascia level and, when necessary, with a Gore-Tex patch. Results Median gestational age was 39 weeks (38-40), and median birth weight was 3100 g (2470-3700). Median age at closure was 6 days (0-20). A central Gore-Tex patch was inserted in 10 cases. Median ventilation length was 26 days (2-78). Full enteral diet was achieved after an average of 33 days (8-82), and median time until discharge from the intensive care unit was 24.5 days (11-85). Nine patients developed sepsis in the postoperative course. In 10 patients, at least 1 associated malformation was diagnosed in the postnatal course, among which cardiac and diaphragmatic defects were the most common. Survival rate was 85.7%. Conclusion Mortality rate of giant omphalocele without chromosomal anomaly or major malformations is low when treated by gradual reduction of the contents. Parents should be informed of the long hospitalization in the intensive care unit at birth, the potential nonthreatening associated malformations to be diagnosed after birth, and the high risk of sepsis.