*Purpose: To define the evolving role of autologous gut reconstruction (AGR) in the management of total parenteral nutrition (TPN)-dependent-chronic gut failure (CGF) patients with special reference to transplantation.

*Methods: A total of 500 CGF-patients with TPN-associated complications were referred for possible gut transplantation versus AGR and were prospectively studied. At a mean age of 47 + 18 years (range: 1.2-88), 80(16%) patients required transplantation and 420(84%) were deemed suitable candidates for AGR. Structure of residual gut, primary cause of gastrointestinal failure, and functional status of the different splanchnic organs guided the decision making process. Transplant recipients received a total of 87 allografts; 64(74%) liver-free and 23(26%) liver-contained with 9% retransplantation rate. AGR patients underwent 650 total procedures; 220(34%) foregut and 430(66%) mid-hindgut. Enhancement of gut physiology and absorption was achieved with jejunal/colonic interposition autografts (n=18), intestinal lengthening (n=45) and enterocyte growth factors (n=16).

*Results: The overall 5-year cumulative patient survival was 80% with re-establishment of nutritional autonomy in 83% of 361 current survivors. AGR was associated with better (p=0.04) survival and transplantation achieved a higher (p=0.07) rate of nutritional autonomy. Both modalities were cost effective and improved quality of life with better results among the AGR population. An outcome predictive model was developed and validated utilizing the initial TPN-total calorie requirements, cause of gut failure and structural status of remaining splanchnic/visceral organs.

*Conclusions: Autologous gut reconstruction along with transplantation are effective therapeutic modalities for CGF-patients. Further improvement in management strategy is foreseen with the reported herein novel predictive model.

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