Background and Aims Crohn's disease (CD) is a chronic and relapsing course with various status of different segments, and there were no investigations comparing the lesion detection between magnetic resonance (MR) and computed tomography (CT) in term of the severity of CD. We aim to assess the performances of diffusion-weighted MR enterography (DW-MRE) and contrast enhanced CT enterography (CTE) for detecting different grade lesions in ileocolonic CD. Methods Forty-one consecutive patients finally diagnosed with ileocolonic CD were included. All the patients prospectively underwent DW-MRE, contrast enhanced CTE, and ileocolonoscopy within 2 weeks. DW-MRE and CTE images were interpreted for the presence or absence of active CD segments by two experienced radiologists independently. Ileocolonic segments (terminal ileum, right colon, transverse colon, left colon, and rectum) were graded as inactive (0-2), mild (3-6), or moderate-severe (>= 7) by the simplified endoscopic score for CD (SES-CD). Diagnostic efficiencies of DW-MRE and CTE for mild and/or moderate-severe CD segments were calculated and compared, using ileocolonoscopy as reference standard. Results According to SES-CD, 190 ileocolonic segments from 41 CD patients were scored as 91 inactive, 68 mild, and 31 moderate-severe CD lesions. The sensitivity of DW-MRE for detecting active from inactive segments was higher than that of CTE, and the specificities of them had no significant differences. As for the subgroup analysis, DW-MRE was more sensitive for mild CD lesions than CTE (76.5% vs 60.3%; P = 0.019), while the sensitivities for moderate-severe CD were similar between these two modalities (96.8% for DW-MRE and 93.5% for CTE; P = 1.00). Conclusions Both DW-MRE and CTE had comparably excellent performances for moderate-severe CD detection; DW-MRE demonstrated better sensitivity in mild lesions compared with CTE and could be more suitable for the diagnosis of mild CD.