Purpose To assess the use of virtual monochromatic images (VMI) for discrimination of affected and non-affected bowel walls in patients with Crohn's disease (CD) as well as to compare mural enhancement between patients with and without CD. Materials and methods This retrospective study included 61 patients (47 with CD, 14 without CD). Attenuation value (AV), signal-to noise ratio (SNR), and contrast-to-noise ratio (CNR) were obtained at VMI energy levels from 40 to 110 keV in 10 keV increment. Analyses were performed among affected and non-affected bowel walls in CD patients, as well as from bowel walls in patients without CD. Image quality and mural enhancement were evaluated at VMI energy levels at 40, 70, and 110 keV. Results At all energy levels of VMI, each quantitative data for AV, SNR, and CNR showed statistically significant difference between diseased and non-diseased bowel walls in CD patients. In the quantitative assessment of patients with and without CD, the optimal AV and SNR were obtained at 40 keV, and the optimal CNR was obtained at 70 keV. For the qualitative assessment, the best image quality and mural enhancement were obtained at 70 keV and 40 keV, respectively. Conclusion VMI are helpful for the differentiation of affected bowel walls in CD patients, providing high diagnostic accuracy.