BACKGROUND Magnetic resonance enterography (MRE) is increasingly attractive as a noninvasive and radiation-free tool for assessing Crohn's disease (CD). Diffusion weighted imaging (DWI) is recommended as an optional MRE sequence for CD by the European Society of Gastrointestinal and Abdominal Radiology, and has shown a superb potential as a quantitative modality for bowel inflammation evaluation. However, the measurement reproducibility of quantitative DWI analysis in MRE has not been ascertained so far. To facilitate the application of quantitative diffusion-weighted MRE in the clinical routine, systematic investigations of the intra and interobserver reproducibility of DWI quantitative parameters should be performed. AIM To evaluate the intra and interobserver reproducibility of quantitative analysis for diffusion-weighted MRE (DW-MRE) in ileal CD. METHODS Forty-four subjects (21 with CD and 23 control subjects) who underwent ileocolonoscopy and DW-MRE (b = 800 s/mm(2)) within one week were included. Two radiologists independently measured apparent diffusion coefficients (ADC) of the terminal ileum and signal intensity ratio (SR) of the terminal ileum to ipsilateral psoas muscle on DWI images (b = 800 s/mm(2)). Between-and with in reader agreements were assessed using intraclass correlation coefficients (ICC), coefficients of variation (CoV), and 95% limits of agreement of Bland-Altman plots (BA-LA LoA). Diagnostic performances of ADC and SR for identifying inflamed terminal ileum from the normal were evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS There were no significant differences in ADC or SR values between the two sessions or between the two radiologists either in the CD or control group (paired t-test, P > 0.05). The intra and interobserver reproducibility of ADC (ICC: 0.952-0.984; CoV: 3.73-6.28%; BA-LA LoA: +/- 11.27% to +/- 15.88%) and SR (ICC: 0.969-0.989; CoV: 3.51%-4.64%; BA-LA LoA: +/- 10.62% to +/- 15.45%) was excellent for CD. Agreement of ADC measurements was slightly less in control subjects (ICC: 0.641-0.736; CoV: 10.47%-11.43%; BA-LA LoA: +/- 26.59% to +/- 30.83%). SR of normal terminal ileum demonstrated high intra and interobserver reproducibility (ICC: 0.944-0.974; CoV: 3.73%-6.28%; BA-LA LoA: +/- 18.58% to +/- 24.43%). ADC and SR of two readers had outstanding diagnostic efficiencies (area under the ROC curve: 0.923-0.988). CONCLUSION Quantitative parameters derived from DW-MRE have good to excellent intra and interobserver agreements with high diagnostic accuracy, and can serve as robust and efficient quantitative biomarkers for CD evaluation.