Introduction: Celiac disease (CD) is an autoimmune enteropathy triggered by gluten ingestion in genetically predisposed individuals. Certain CD patients have persistent symptoms despite strict adherence to a gluten free diet (GFD) for more than 6-12 months, and are designated as non-responsive (NRCD). A fraction of these NRCD patients have refractory CD (RCD), but the remainder may have irritable bowel syndrome (IBS)-type symptoms like abdominal pain and diarrhea. There are no studies to date that examine constipation in the context of NRCD caused by either IBS-constipation predominant (C) or chronic idiopathic constipation (CIC). We have identified a subset of NRCD patients in whom constipation is the main etiology of persistent symptoms and present their characteristics. Methods: We performed retrospective chart review of 35 non-refractory NRCD patients with histological Marsh scoring of 0-1 on biopsy (normal to near-remission) between 2016 and 2020. Patients were defined as having NRCD if they had a biopsy-confirmed diagnosis of CD but had gastrointestinal symptoms despite a strict GFD for over 6 months. This group was separated further into patients with constipation-related NRCD (c-NRCD, 24 patients) and those with non-constipation related NRCD (nc-NRCD, 11 patients) based on Rome IV criteria and/or improved symptomatic response to bowel regimen. Results: 68.5% of patients with non-refractory NRCD had c-NRCD. The median age of the c-NRCD cohort was overall younger as compared to the nc-NRCD cohort. Most patients in both groups had normalized celiac serology (>70%). Constipation and bloating were the predominant symptoms in the c-NRCD group while diarrhea was the predominant symptom in nc-NRCD. Abdominal x-ray was performed in all of the suspected c-NRCD group as compared to nc-NRCD group (36.4%). Most c-NRCD patients had at least a moderate stool burden radiographically (70.8%) as read by the same radiologist whereas most nc-NRCD patients had no stool burden seen. Conclusion: Constipation is a significant driver of persistent symptoms in CD leading to NRCD, in part due to the lower fiber content of a GFD. Clinicians should screen all NRCD patient based on the Rome IV criteria and consider an abdominal x-ray followed by the initiation of a bowel regimen if overlap constipation is suspected. This can improve the health outcomes in these patients and provide cost-effectiveness prior to employing other modalities like breath tests or infectious evaluation.Figure 1.: Flow Chart for Constipation versus Non-constipation related Non-Responsive Celiac Disease (NRCD).Table 1.: Demographic and Clinical Features of Patients with Constipation-related or Non-Constipation-related Non-Refractory Non-Responsive Celiac Disease (NRCD)