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Context.--Graft-versus-host disease of the gastrointestinal tract is a common complication of hematopoietic stem cell transplant associated with significant morbidity and mortality. Accurate diagnosis can be difficult and is a truly clinicopathologic endeavor. Objectives.--To assess the diagnostic sensitivity of gastrointestinal graft-versus-host disease using the 2015 National Institutes of Health (NIH) histology consensus guidelines and to analyze histologic findings that support the guidelines. Design.--Patients with allogeneic hematopoietic stem cell transplants were identified via a retrospective search of our electronic medical records from January 1, 2005, to January 1, 2011. Endoscopies with available histology were reviewed by 2 pathologists using the 2015 NIH guidelines. The clinical diagnosis was used as the gold standard. A nontransplant set of endoscopic biopsies was used as a control. Results.--Of the 250 total endoscopies, 217 (87%) had a clinical diagnosis of gastrointestinal graft-versus-host disease. Use of the NIH consensus guidelines showed a sensitivity of 86% and a specificity of 65%. Thirty-seven of 58 (64%) cases with an initial false-negative histopathologic diagnosis were diagnosed as graft-versus-host disease on our review. Conclusions.--Use of the NIH histology consensus guidelines results in a high sensitivity and specificity, thereby decreasing false-negatives. Additionally, use of the NIH guidelines aids in creating uniformity and diagnostic clarity. Correlation with clinical and laboratory findings is critical in evaluating the differential diagnosis and to avoid false-positives. As expected, increased apoptosis with decreased inflammation was associated with a pathologic diagnosis of graft-versus-host disease and supports the NIH guidelines. doi: 10.5858/arpa.2017-0054-0A, Graft-versus-host disease (GVHD) of the gastrointestinal (GI) tract is a common complication of hematopoietic stem cell transplant (HSCT) and is associated with significant morbidity and mortality. (1-6) Graft-versus-host disease develops [...]