We present 3 cases of Crohn's disease that developed in patients with previously diagnosed short bowel syndrome from another cause. There are characteristics unique to patients with short bowel syndrome that may increase their likelihood to develop Crohn's disease, based on current concepts of the pathophysiology of inflammatory bowel disease. These patients may have a higher than average prevalence of small intestinal bacterial overgrowth. This may lead to an increase in bacterial translocation and dysregulation of the intestinal immune response. In addition, these patients often require parenteral nutrition (PN) because of macronutrient and micronutrient deficiencies. Some patients receiving PN, particularly those with bowel obstructions, may be at risk for septicemia due to bacterial translocation. It is thought that PN may enhance intestinal dysmotility and impair gut immunity, contributing further to an antigenic immune response in the intestinal immune system, although supporting data is lacking. Finally, studies have demonstrated that patient's with Crohn's disease have a shorter bowel length before any intestinal resections and not related to disease activity. Although the significance of this is unclear, a shorter bowel length may potentially predispose people to the development of Crohn's disease via an alteration of intestinal motility and intestinal flora.