Acute graft-versus-host disease (GVHD) is a major complication following allogeneic stem cell transplantation (allo-SCT) and carries a high morbidity and mortality rate [1]. This disease may affect the skin, liver, and gastrointestinal tract (acute GI GVHD). Mismatched histocompatibility antigens cause graft T cells to attack the host’s tissues in acute GI GVHD. Histologic findings in the intestine include crypt epithelial cell apoptosis, crypt destruction, and variable lymphocytic infiltration of the epithelium and lamina propria (Fig. 22.13 ). Severe GVHD (Table 36.1) affects the small bowel, causing extensive damage with a large spectrum of endoscopic findings [3]. Patients with acute GI GVHD have a higher mortality than patients without acute GI GVHD [4]. Treatment of acute GI GVHD requires aggressive immunosuppressive therapy, which is associated with infectious complications.