BACKGROUND The purpose of this study was to evaluate the outcome of 19 patients who underwent intestinal transplantation (ITx) for intestinal failure. METHODS The 19 patients who underwent primary ITx between December 2000 and May 2003 were prescribed three different immunosuppressive protocols that included daclizumab, alemtuzumab, and antithymocyte globulin induction, respectively. A mucosal surveillance protocol for early detection of rejection consisted of zoom video endoscopy and serial biopsies associated with orthogonal polarization spectral imaging. Retrospective review of the clinical records was performed to assess the impact of new modalities of immunosuppression and intestinal mucosal monitoring on patient outcomes. RESULTS All patients were adults (mean age 35.8 years). Etiology of intestinal failure included chronic intestinal pseudo-obstruction (n = 6), intestinal angiomatosis (n = 1), Gardner syndrome (n = 2), intestinal infarction (n = 8), radiation enteritis (n = 1), and intestinal atresia (n = 1). All patients experienced complications from total parenteral nutrition (TPN). Thirteen patients (68.4%) received isolated small bowel, whereas six (31.6%) received multivisceral grafts with or without the liver. Thirteen of 19 patients experienced at least one episode of rejection (68.4%). Most ACR episodes were treated with steroid boluses and resolved completely within 5 days. The overall 1-year patient survival was 82%. All living patients are in good health with functioning grafts having been weaned off TPN after a mean of 23.7 days post-ITx. DISCUSSION Advances in immunosuppressive therapy with early detection and prompt treatment of rejection episodes make ITx a valuable treatment option for patients with intestinal failure and TPN-related life-threatening complications.