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Diffusion-weighted imaging (DWI) is a novel technique to evaluate bowel inflammation in Crohn's disease (CD). It is unknown whether and how DWI adds to the accuracy of conventional magnetic resonance enterography (MRE).Fifty consecutive adults suspected of CD prospectively underwent clinical assessment, conventional MRE and DWI at b = 900 sec/mm2 without water enema, and ileocolonoscopy within 1 week. MRE images were interpreted with proper blinding. Forty-four patients finally diagnosed with CD (male:female, 34:10; 26.9 ± 6.1 yr) were analyzed. The per-segment accuracy of MRE for diagnosing active CD was assessed in the terminal ileum, right colon, and rectum using location-by-location matching with endoscopy as the reference standard.The study evaluated 58 bowel segments with deep or superficial ulcers, 34 with aphthae, erythema, or edema only, and 35 without inflammation. Conventional MRE + DWI was more sensitive for bowel inflammation than conventional MRE alone (83% [76/92] versus 62% [57/92]; P = 0.001) largely because of additional detection of aphthae, erythema, or edema. The sensitivities for deep and overt ulcers were similar regardless of DWI, ranging from 88% to 97%. Conventional MRE + DWI was less specific than conventional MRE alone (60% [21/35] versus 94% [33/35]; P < 0.001), mostly because of many false positives in the colorectum. Positive DWI findings in the bowel showing active inflammation on conventional MRE were associated with higher Crohn's disease endoscopic index of severity score (P = 0.021) and deep ulcers (P = 0.01; diagnostic odds ratio, 12).DWI performed without water enema is not useful for incremental detection of bowel inflammation. DWI may help identify more severe inflammation among bowel segments showing active inflammation on conventional MRE.