Intestinal transplantation (Itx) is increasingly being performed to treat patients with irreversible intestinal failure. Acute graft-versus-host disease (GVHD) after Itx is a life-threatening complication which can progress to organ failure, systemic complications and death. The purpose of this study was to assess the diagnostic and prognostic role of histological changes as demonstrated by skin biopsy for acute GVHD after Itx. A porcine model of orthotropic Itx and bone marrow transplantation with tacrolimus-based immunosuppression was used to assess any correlation between acute graft cellular rejection and skin histological findings for the prediction of GVHD. Skin and small intestinal biopsies were histologically assessed on postoperative days 0, 15, 30, 45, and 60 and analyzed and classified as grade 1 to 4. A linear correlation was observed between the histological grading values of skin biopsy changes and the histological grading values of small intestinal biopsy changes (Kendall's tau_b was 0.855 for the Itx group and 0.730 for the Itx BM group. In conclusion, our findings emphasize the diagnostic and prognostic value of skin biopsy analysis for acute GVHD after Itx.