The significance of upper gastrointestinal tract (UGI) acute GVHD (aGVHD) compared with other grade II aGVHD is not clearly defined. We compared the outcomes of patients with grade II aGVHD with or without biopsy-proven UGI involvement in three groups: grade II aGVHD without UGI (n=178), grade II aGVHD with UGI and other sites (n=102) and isolated UGI aGVHD (n=32). The overall response (ORR) to steroids at day 28 differed among the three groups (76, 67 and 91%, respectively, P=0.01), but was only marginally different in direct comparison with those without or with UGI aGVHD (P=0.07) or with isolated UGI aGVHD (P=0.06). In multivariate analysis, as compared with grade II aGVHD patients without UGI involvement, those with UGI involvement and those with isolated UGI aGVHD had similar risks of chronic GVHD, relapse and non-relapse mortality and similar disease-free survival and overall survival. Our data suggest that patients with UGI aGVHD have similar outcomes as those without UGI involvement, supporting the view that UGI aGVHD should still be included as a grade II-defining event.