Objectives Growing evidence supports the view that the diagnosis of coeliac disease (CD) can be made by serological tests alone, although this approach is still not widely accepted. We previously showed in retrospective and prospective studies that in adults an IgA-tissue transglutaminase antibody cut-off can be defined above which the positive predictive value for CD is 100%. Following a change in the analytical method for measuring the antibody, our objectives were to re-examine this finding in a larger series of adults to ascertain whether a diagnosis of CD can be reliably made in a proportion of patients without the need for small bowel biopsy and to re-evaluate the diagnostic guidelines used in our centre. Patients and methods A retrospective analysis was done in an unselected series of 270 adult patients who had small bowel biopsies and serum IgA-tissue transglutaminase antibody levels measured from 2009 to 2014. Results At an IgA-tissue transglutaminase antibody cut-off greater than 45 U/ml (>8 x upper limit of normal + 2SDs) the positive predictive value for CD in this cohort was 100%; 40% of cases were above this cut-off. Conclusion We have verified that a diagnosis of CD can be reliably made in a high proportion of adults based on serology alone using the IgA-tissue transglutaminase antibody method specified. These results add to the body of evidence that small bowel biopsy should no longer be considered mandatory for the diagnosis of CD. On the basis of these results the diagnostic guidelines in our centre have been modified. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.