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Introduction The British Society of Gastroenterology (BSG) advises obtaining at least four duodenal biopsies, including one from the duodenal bulb, when investigating suspected coeliac disease (CD). However, if the patient has negative serology prior to endoscopy, duodenal biopsy may be unnecessary. We evaluated duodenal biopsy practice within Sheffield Teaching Hospitals (STH) to assess adherence to guidance and evaluate serology negative biopsy practice.Methods We conducted a retrospective service evaluation of adult oesophago-gastro-duodenoscopies (OGDs) undertaken at STH between 2023 and 2024 for indications compatible with suspected CD (anaemia, diarrhoea, weight loss and positive tTG). Incomplete, emergency and therapeutic procedures were excluded, as well as those where duodenal biopsies for CD would be inappropriate (e.g., malignancy).Data collected included site, endoscopist, serological status, number and location of duodenal biopsies, previous OGD history and histological outcome. Guideline adherence was defined according to BSG 2014 recommendations, and diagnostic yield was defined as histological confirmation of CD. Associations were assessed using chi-squared testing and non-parametric tests for biopsy count.Results 4301 OGD’s were included in this analysis. Of these, 36.2% (1557/4301) had negative pre-endoscopy coeliac serology but still underwent duodenal biopsy, with 21.3% (331/1557) having a prior OGD in the past 5 years. This resulted in at least 5047 duodenal biopsies taken in a low-yield population. Only 0.13% (2/1557) were diagnosed with seronegative CD. Based on a local micro-costing estimate of £88 per duodenal biopsy, up to £444,136 could be attributed to serology-negative biopsy practice during the study period.Conversely, 16.4% (706/4301) procedures met full BSG biopsy guidance. CD was confirmed in 6.7% patients (287/4301). Diagnostic yield was significantly higher when guidelines were followed: CD was diagnosed in 38.4% of guideline adherent procedures compared with 0.4% of non-adherent procedures. Each additional biopsy increased the odds of confirming CD over 2.5-fold (95% CI 2.32–2.80; p<0.001).Conclusion Our data suggests clinicians in real world clinical practice are failing to act on negative serology (and may not even be aware of the result). Biopsy avoidance based on negative serology has significant cost-benefits. Equally, adherence to BSG duodenal biopsy guidance in suspected CD is strongly associated with diagnostic yield. Greater emphasis on serology-guided biopsy selection may improve diagnostic efficiency, reduce cost and optimise endoscopy and pathology resources.