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Nonresponsive celiac disease (NRCD) is a common problem affecting from 7% to 30% ofceliac patients. Because NRCD comprises varied and poten-tially morbid entities, efficient and cost-effective patientcare requires knowledge of the specific causes of this dis-order. The aim of this study was to determine the commonetiologies of NRCD in a tertiary referral center. Methods: All cases of biopsy examination–proven celiac disease (CD)seen at our institution over the preceding 5 years wereincluded in this study. NRCD was defined as a failure torespond to at least 6 months of treatment with a gluten-freediet or the re-emergence of symptoms or laboratory abnor-malities typical of CD while still on treatment with a gluten-free diet. Results: A total of 113 patients with NRCD meeting the earlier-described criteria were seen from atotal of 603 patients with CD (19%), however, amongpatients for whom we provided primary specialist carethe incidence of NRCD was 10% (P < .001). Gluten expo-sure was the most common cause of NRCD (36%), fol-lowed by irritable bowel syndrome (22%), refractory CD(10%), lactose intolerance (8%), and microscopic colitis(6%). The mean immunoglobulin A tissue transglutami-nase level in the gluten-exposed group was 67 vs 17 U/mL(normal, <20) for other diagnoses (P < .05). Weight lossand male sex were highly predictive of refractory CD (P <.05 and < .001, respectively). Conclusions: NRCD is a common phenomenon affecting 10%–19% of celiac patients.A limited number of etiologies account for the majority ofcases. Clinical factors may be used to guide evaluation