Background: The aim of this study was to assess the impact of an amino acid-based complete infant formula on enteral feeding tolerance and parenteral nutrition requirement in children with severe short bowel syndrome. Methods: Four children (23 months-4.75 years) with short bowel syndrome who required long-term parenteral nutrition due to persistent feeding intolerance while receiving an extensively hydrolyzed formula were assessed before and after the commencement of an amino acid-based complete infant formula for a mean follow-up period of 48 months (range 39-51 months). Assessment included clinical monitoring of feeding tolerance and nutritional status, biochemistry, stool analysis, skin-prick testing to common food antigens, esophagogastroduodenoscopy and colonoscopy or jejunoscopy with biopsies, and measurement of disaccharidase levels and intestinal permeability. Results: All patients ceased parenteral nutrition within 15 months as a result of decreased stool output and resolution of vomiting. Patients had a reduction in hospitalization (mean: 198 versus 98 days/patient/year), episodes of proven(mean: 4.3 versus 3.3/patient/year) and suspected (mean: 6.5 versus 4.0/patient/year) bacterial sepsis and central line insertions (mean: 2.5 versus 1.5/patient/year). Intestinal permeability to lactulose fell markedly(mean: 69% versus 2.7%). Disaccharidase levels increased in all three patients undergoing repeat studies. Conclusions: An amino acid-based complete infant formula improved feeding tolerance and eliminated the need for parenteral nutrition in four children with short bowel syndrome who had previously required long-term parenteral nutrition. The clinical improvement was mirrored by improvement in measurements of intestinal function.