Purpose To evaluate the accuracy of MRI-quantified small bowel motility for Crohn disease activity against endoscopic and histopathologic reference standards. Materials and Methods For this prospective study, 82 participants (median age, 31 years; range, 16 to 70 years; 42 males [median age, 31 years; range, 17 to 70 years] and 40 females [median age, 31 years; range, 16 to 63 years) underwent colonoscopy and MR enterography within 14 days (from October 2011 to March 2014) at two centers. The Crohn disease endoscopic index of severity (CDEIS), histopathologic activity score (endoscopic biopsy acute histologic inflammatory score [EAIS]), and MR index of activity (MaRIA) were scored in the terminal ileum. Terminal ileal motility was quantified by using an image registration based-motility assessment algorithm (hereafter, Motility). Sensitivity and specificity of Motility (˂0.3 arbitrary units) and MaRIA (≥7 and ≥11) for disease activity (CDEIS ≥4 or EAIS ≥1) were compared by using the McNemar test. Receiver operating characteristic curves were constructed and areas under the curve were compared. Motility was correlated with reference standards by using Spearman rank estimates. Results Terminal ileal Motility was negatively correlated with EAIS (r =-0.61; 95% confidence interval [CI]: 0.7, -0.5) and CDEIS (r = -0.59; 95% CI: 0.7, -0.4). With CDEIS as the standard of reference, Motility had higher sensitivity than did MaRIA (≥11) (93% vs 78%, respectively; P = .03), but lower specificity (61% vs 81%, respectively; P = .04). With EAIS as the standard of reference, Motility had higher sensitivity than did MaRIA (≥7) (92% vs 75%, respectively; P = .03) but similar specificity (71% vs 74%, respectively; P >.99). The area under the receiver operating characteristic curve for Motility was 0.86 and 0.87 with CDEIS and EAIS as the standard of reference, respectively. Conclusion The terminal ileal Motility score showed good agreement with endoscopic and histopathologic activity in Crohn disease. © RSNA, 2018 Online supplemental material is available for this article.