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Recent reports suggest that the duodenal bulb may be the only site to demonstrate villous atrophy (VA) in celiac disease. However, there is a paucity of data from newly diagnosed adult celiac patients and no data from those patients with established celiac disease. The objective of this study was to compare the histological findings in the duodenal bulb and distal duodenum of patients with adult celiac disease (newly diagnosed or established) against controls.A total of 461 patients were prospectively recruited. Biopsies were graded using the Marsh criteria.In all, 461 patients (300 females and 161 males) with median age 51 years were analyzed. In all, 126 had newly diagnosed celiac disease, 85 established celiac disease, and 250 controls. New diagnosis celiac disease (9%,P<0.0001) and established celiac disease (14%,P<0.0001) were more likely than controls to have VA in the bulb alone. Overall, when comparing the histological lesion of the bulb against the distal duodenum, 31/85 with established celiac disease (P<0.0001) and 21/126 newly diagnosed (P=0.0067) had a discrepancy in the severity of the lesion between the two sites compared with 18/250 controls. In all, 24/31 with established celiac disease and 16/21 newly diagnosed had the more severe lesion in the bulb.VA may be present only in the duodenal bulb. This study suggests that the optimal assessment of patients in whom celiac disease is suspected (with positive serology) and those with established celiac disease requires a duodenal bulb biopsy in addition to distal duodenal biopsies.