Introduction: Closure of giant omphalocele can present a surgical challenge. Neither silo, skin flap, nor primary closure has been successful in treating all patients. We present a novel application of the vacuum-assisted closure (VAC) device, which allows for improved results in these difficult cases. Methods: The VAC device (KCI, San Antonio, Tex) consisted of a sponge applied directly to the bowel and liver, covered with impermeable transparent dressing, and attached to a low negative pressure system. The sponge was changed every 3 to 5 days under local sedation. Patients: All 3 patients had giant omphaloceles. The first infant, a 34 week gestational age (WGA) male, was initially treated with silo reduction, which disrupted after 21 days. The large mass of bowel and liver made primar y closure impossible. The VAC was applied for 45 days. The viscera was easily reduced and subsequently covered with acellular dermal matrix (AlloDerm). The VAC was reapplied, and the small remaining defect was skin-grafted. The second male infant was a 34 WGA male infant who became septic after failure of prosthetic mesh closure. The VAC was applied for 22 days after removal of the mesh. The infection resolved, and the defect size was reduced, allowing for skin flap closure. Mesh infection and development of an enterocutaneous fistula in the last patient, a 37 WGA female child, were treated by mesh removal and application of the VAC for 36 days. The VAC allowed for control of the fistula output and development of a healthy granulation bed. Results: Vacuum-assisted closure was associated with (1) rapid shrinkage and reduction of the viscera (22-45 days); (2) cleansing of the wound; (3) excellent granulation; (4) maintenance of a sterile environment; and (5) ease of use, with changes possible at the bedside. Conclusion: The VAC device should be considered a safe and effective alternative in treating complicated cases of giant omphalocele until a more definitive closure method can be used. Introduction: Closure of giant omphalocele can present a surgical challenge. Neither silo, skin flap, nor primary closure has been successfully treated in all patients. We present a novel application of the vacuum-assisted closure (VAC) device, which allows for improved results In these difficult cases. Methods: The VAC device (KCI, San Antonio, Tex) consisted of a sponge applied directly to the bowel and liver, covered with impermeable transparent dressing, and attached to a low negative pressure system. The sponge was changed every The first infant, a 34 week gestational age (WGA) male, was initially treated with silo reduction, which disrupted after 21 days. The large mass of bowel and The VAC was applied for 45 days. The viscera was easily reduced and subsequently covered with acellular dermal matrix (AlloDerm). The VAC was reapplied, and the small remaining def The second male infant was a 34 WGA male infant who became septic after failure of a prosthetic mesh closure. The VAC was applied for 22 days after the removal of the mesh. The infection resolved, and the defect size was reduced, allow for skin flap closure. Mesh infection and development of an enterocutaneous fistula in the last patient, a 37 WGA female child, were treated by mesh removal and application of the VAC for 36 days. The VAC allowed for control of the fistula output and development of a healthy granulation bed. Results: Vacuum-assisted closure was associated with (1) rapid shrinkage and reduction of the viscera (22-45 days); (2) cleansing of the wound; (3) excellent granulation; of a sterile environment; and (5) ease of use, with changes possible at the bedside. Conclusion: The VAC device should be considered a safe and effective alternative in treating complicated cases of giant omphalocele until a more definitive closure method can be used.