Graft-versus-host disease and disease relapse are the 2 major causes of failure of allogeneic hematopoietic stem cell transplantation (SCT). Ideally, patients who undergo transplantation for malignancies would receive the minimum effective acute graft-versus-host disease (GVHD) prophylaxis to maximize the graft-versus-tumor potential of the allogeneic SCT. Tailoring acute GVHD prophylaxis to the risk for each patient has long been a goal for SCT, but no practical way to adjust acute GVHD prophylaxis has been developed. In murine models of acute GVHD, gut damage from the preparative regimen resulting in the release of many mediators is crucial for initiation of acute GVHD. Using diarrhea as a marker of gut damage, we performed a retrospective study of patients at the Johns Hopkins Hospital given matched sibling transplants for chronic myelogenous leukemia to determine whether gut damage during the preparative regimen is predictive of the development of acute GVHD in humans. Logistic regression models were used to perform the retrospective analysis of the relation of diarrhea during the preparative regimen to a significant acute GVHD grade. This work demonstrated a significant positive correlation between the sum of diarrhea on days 4 to 7 after SCT and acute GVHD and showed a borderline significant positive correlation between the sum of diarrhea on days 1 to 3 and acute GVHD. This is the first correlation demonstrated between gut damage during the preparative regimen and acute GVHD severity in humans. This suggests that damage from the preparative regimen could be used as a marker for the risk of acute GVHD. Prospective trials would have to test whether acute GVHD prophylaxis could be adjusted according to this risk. This may result in a greater graft-versus-tumor effect for patients with less risk of acute GVHD.