BACKGROUND: Expected benefits of gluten-free diet (GFD) in coeliac patients include healing of small intestinal mucosa, but it remains unclear to what extent this benefit is achieved in adults. AIM: To assess factors affecting histological outcome of GFD in a large cohort of adult coeliac patients. METHODS: We extracted information on 465 consecutive coeliac patients studied before and during GFD. RESULTS: Duodenal biopsies at diagnosis were classified as Marsh I in 11, II in 25 and III in 429 cases. After a median 16 months GFD, 38 (8%) patients had histological 'normalization', 300 (65%) had 'remission' with persistent intraepithelial lymphocytosis, 121(26%) had 'no change' and 6 (1%) had 'deterioration'. Coeliac disease related serology was negative in 83% of patients with Marsh III lesion during GFD. Male gender and adherence to GFD were independently associated with histological 'normalization' and 'remission'. Persistence of intraepithelial lymphocytosis was not associated with human lymphocyte antigen gene dose or with Helicobacter pylori infection. CONCLUSIONS: Complete normalization of duodenal lesions is exceptionally rare in adult coeliac patients despite adherence to GFD, symptoms disappearance and negative CD related serology. Control biopsies are mandatory to identify lack of response to gluten-free diet.