This prospective pilot study aimed to evaluate the predictive value of (18)F-FDG PET/CT for early diagnosis of acute gastrointestinal GVHD (GI-GVHD). In all, 42 consecutive patients who received allo-SCT were included. (18)F-FDG PET/CT was systematically performed at a median of 28 (range, 24-38) days after allo-SCT. (18)F-FDG PET/CT data review was positive in 15 cases (36%) (9 true positive (TP) cases and 6 false positive (FP) cases) and negative in 27 cases (64%; 26 true negative (TN) cases and 1 false negative (FN) case) at visual analysis. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of (18)F-FDG PET/CT for the diagnosis of acute GI-GVHD were, respectively, 81%, 90%, 60%, 96% and 83%. There were no significant differences of SUVmax values between grade 1-2 GI-GVHD and severe grade 3-4 GI-GVHD. Overall, these preliminary findings suggested that the inflammatory activity of the gastrointestinal tract associated with acute GI-GVHD could be assessed by (18)F-FDG PET/CT suggesting that noninvasive (18)F-FDG PET/CT could become a valuable examination to be performed shortly before endoscopy to map acute GI-GVHD lesions, guide the biopsy sites and choose the appropriate endoscopic procedure, especially in those asymptomatic patients with a positive (18)F-FDG PET/CT.