BackgroundIntestinal transplantation (ITx) has evolved into a viable option for patients suffering from intestinal failure (IF). As graft and patient survival increase, we enter a new era where re-transplantation (re-ITx) is increasingly considered. Re-ITx grafts historically are less successful than their primary counterpart. While re-ITx is challenging for the obvious reasons of a re-do operation, there are potentially modifiable pre-transplant clinical and technical factors which are not yet understood. MethodsWe conducted an in-depth review of our re-ITx experience at a high volume transplant center, and describe unique predictors associated with improved outcomes. ResultsThere were 132 primary ITx performed from 1991-2021; 44 primary ITx failed (33%) and of those, 25 (56%) were re-transplanted within the time of this retrospective review. The median time to re-ITx was 13 months (5 days–6 years). I-ITx recipients were more commonly re-transplanted with liver-inclusive grafts (64%). Re-ITx recipients were more often male (p=0.05), had positive crossmatch (p=0.01), PRA>20% (p=0.03), and underwent ATG-induction (p=0.00). The mean graft survival in months in primary ITx was 74.0 (0.0 - 303.2) and in re-ITx was 60.0 (0.0 - 155.83) (p=0.37). The leading indication for re-ITx was ACR of the primary graft (64%). Successful re-ITx (graft survival >1 year) was significantly associated with ATG-induction (p=0.003). Liver-inclusive grafts demonstrated increased 1-year survival compared with liver-free grafts, but not significantly (primary ITx: 72% vs 55%; re-ITx: 75% vs 57%). Enterectomy of the primary graft prior to re-ITx appeared to increase overall graft survival after re-ITx, but not significantly (70 vs 40 months, p=0.17). Enterocolonic continuity was associated with overall longer graft survival after re-ITx (95 vs 40 months, p=0.03). ConclusionWe demonstrate several factors to consider when evaluating patients for re-ITx, a multicenter study is needed to understand how patient selection, clinical management, and technical modifications can improve outcomes after re-ITx.