To prospectively investigate how Buscopan affects the diagnosis of bowel inflammation by diffusion-weighted imaging MR enterography (DWI-MRE) in Crohn's disease (CD). Thirty CD patients without previous bowel surgery underwent DWI-MRE (b = 900 sec/mm(2)) before and after intravenous Buscopan. The 30 patients were randomly divided into two groups; using a crossover design, interpretations were made regarding the presence of restricted mural diffusion (i.e., bowel inflammation) in nine bowel segments in two separate reading sessions by two readers. The readers also judged restricted mural diffusion extent in each bowel segment on two side-by-side DWI-MRE images with a random right-to-left order. Ileocolonoscopy and conventional MRE interpreted by an expert panel were reference standards. We analyzed 262 bowel segments. DWI-MRE without Buscopan significantly decreased sensitivity for both readers (58.8 % vs. 72.9 %, P = 0.046; 57.6 % vs. 85.9 %, P = 0.001) and did not significantly increase specificity (P = 0.085 and 0.396). Two readers noted that 28.6 % and 23.3 % of 262 bowel segments had greater diffusion restriction extent on DWI-MRE with Buscopan compared with DWI-MRE without Buscopan (P < 0.001) and 68.7 % and 74 %, respectively, had similar extent between them. Omitting Buscopan caused a greater loss in sensitivity of DWI-MRE than false-positive reduction for diagnosing bowel inflammation in CD. aEuro cent Omitting Buscopan significantly decreases DWI-MRE sensitivity for diagnosing bowel inflammation in CD. aEuro cent Increase in the corresponding DWI-MRE specificity by omitting Buscopan is less apparent. aEuro cent DWI-MRE without Buscopan underestimates the extent of bowel inflammation in CD.