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Background: The diagnosis of proximal small bowel involvement in Crohn's disease (CD) can be challenging at magnetic resonance enterography (MRE). The inflammatory process in CD can be associated with peri-intestinal inflammatory reactions, including the presence of inflamed mesenteric lymph nodes. Objectives: To evaluate the significance of inflamed mesenteric lymph nodes adjacent to the jejunum at MRE in CD and the association with proximal bowel disease as detected by video capsule endoscopy (VCE). Design: This retrospective study was performed in two tertiary medical centres, and included 64 patients with CD who underwent MRE as well as VCE within 1 year. Methods: Data were collected for examinations performed between August 2013 and February 2021. MRE images were independently reviewed by radiologists who were blinded to the clinical data. Association between the presence of mesenteric lymph nodes adjacent to jejunum at MRE and disease activity according to VCE Lewis scores of proximal small bowel was examined. Results: VCE detected proximal disease in 24/64 patients (37.5%). Presence of regional lymph nodes in the jejunal mesentery was significantly associated with jejunal disease as seen on VCE (p < 0.001). Of the 20 patients who had proximal mesenteric lymph nodes at MRE, 15 (75%) had jejunal disease at VCE (sensitivity, 62.5%; specificity, 87.5%; and negative and positive predictive values, 79.5 and 75%, respectively). The number of regional lymph nodes was positively correlated with jejunal disease (mean: 2.63 ± 2.90 versus 0.78 ± 2.60, p = 0.01). Other MRE features of lymph nodes were not significantly predictive of jejunal CD. Conclusion: In patients with CD, inflamed regional lymph nodes in the jejunal mesentery at MRE can be valuable to suggest proximal small bowel disease, even when bowel wall features at imaging do not suggest disease involvement. Plain language summary: The diagnosis of proximal small bowel involvement in Crohn's disease (CD) can be challenging at magnetic resonance enterography (MRE). We analysed MRE examinations in patients with CD for the presence of lymph nodes adjacent to the proximal small bowel. We included 64 patients with CD who had MRE examinations and video capsule endoscopy (VCE) examinations within 1 year. Of 64 patients, 24 had proximal small bowel disease according to VCE. We found that of 20 patients who had regional mesenteric lymph nodes in the jejunal mesentery at MRE, 15 had proximal bowel disease involvement. We also found that patients with jejunal disease had a larger number of regional lymph nodes compared to patients without jejunal disease. All but one patient had normal appearing bowel at MRE. But, using regional mesenteric lymphadenopathy at MRE as an indicator for disease, 15/24 (62.5%) patients with proximal small bowel disease were detected. We therefore conclude that regional mesenteric lymph nodes assessment at MRE can aid diagnose proximal bowel disease, even when the proximal bowel looks normal at imaging. Presence of proximal mesenteric lymph nodes at MRE in patients with CD possibly warrant further investigation of the proximal small bowel by endoscopic measures. [ABSTRACT FROM AUTHOR]