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Introduction:  The U.K. National Institute for Health and Clinical Excellence (NICE) specify the following indications for performing rectal biopsy to rule out Hirschsprung's disease (HSD): (1) passage of meconium > 48 hours; (2) constipation since first few weeks of life; (3) chronic abdominal distension with vomiting; (4) family history of HSD; and (5) faltering growth in addition to any other indication. The aim of this study was to assess the compliance of a tertiary referral center with the current U.K. NICE guidelines for performing rectal biopsies to rule out HSD. Secondary aims included assessing alternative indications and complication rates.Materials and Methods:  Retrospective analysis of patients undergoing open or suction rectal biopsies to investigate HSD, from 2009 to 2014.Results:  A total of 188 patients underwent 214 biopsies (suction: n = 154, open: n = 60). Note that 128 patients (68.1%) had biopsies indicated by NICE. A total of 84.4% of indicated biopsies were ganglionic versus 91.7% of unindicated biopsies (p = 0.17). Twenty-five patients were diagnosed with HSD (mean age: 13.2 weeks, range: 3 days-3.2 years). Only 80% of HSD patients had NICE-indicated biopsies. Presentations for patients with biopsies not indicated by NICE included constipation, distension, and vomiting that did not strictly meet the guidelines. The majority of biopsies were uncomplicated (suction 82.5% vs. open 95.0%)-inadequate/indeterminate histology was the most common complication (16.2% suction vs. 5% open).Conclusion:  A significant number of unindicated biopsies were performed, the majority of which were ganglionic. Rectal biopsies are generally safe and strict adherence to the NICE guidelines could have led to missed HSD diagnoses with potential significant morbidity and mortality. [ABSTRACT FROM AUTHOR]