Management of children with intestinal failure is optimized by interdisciplinary coordination of parenteral and enteral nutrition support, medical management of associated complications, surgical lengthening procedures, and intestinal transplantation. Three hundred eighty-nine pediatric patients have been referred to our center for interdisciplinary assessment of intestinal failure since 1996 (median age=1 year; range 1 day-28.8 years). Factors predictive of weaning from parenteral nutrition without transplantation included increased mean bowel length for patients with gastroschisis (44 vs. 23 cm, p<0.05) and atresia (35 vs. 20 cm, p<0.01) and lower mean total bilirubin for patients with NEC (6.1 vs. 12.7 mg/dL, p<0.05). Others were also more likely to survive if referred with a lower mean total bilirubin (NEC, 7.9 vs. 12.7 mg/dL, p<0.05; pseudo-obstruction, 2.3 vs. 16.3 mg/dL, p<0.01). Patients weaned from parenteral nutrition by 2.5 years after referral achieved 95% survival at 5 years vs. 52% for those not weaned. Bowel lengthening procedures were performed on 25 patients. Eight subsequently weaned from parenteral nutrition without transplantation. Aggressive medical and nutritional intervention along with early referral, intestinal lengthening procedures, and intestinal transplantation in children with intestinal failure dependent on parenteral nutrition can result in the achievement of enteral autonomy and improved survival.