Background Crohn's disease (CD) is characterised by chronic gastrointestinal inflammation with relapsing-remitting behaviour and often requires endoscopic and/or radiologic assessment. Objective The objective of this study was to compare the diagnostic accuracy of intestinal ultrasound (IUS) and magnetic resonance enterography (MRE) for the assessment of disease activity in CD using a simple endoscopic score for CD as a reference standard. Patients and methods A prospective observational study was carried out in 71 consecutive adult patients with known CD, attending our tertiary inflammatory bowel disease clinic, between November 2014 and July 2016. Ileocolonoscopy, IUS and MRE were performed within 1 month prospectively. The simple endoscopic score-CD 0-2 was accepted as remission. Results The sensitivity of IUS and MRE for detecting endoscopic activity was found similar with regard to bowel wall thickening and mesenteric fibrofatty proliferation (P>0.05). The overall accuracy for detecting mural lesions was similar between IUS and MRE. When mural lesions were analysed, the sensitivity of MRE in detecting the loss of wall stratification and stenosis was significantly higher than IUS (P<0.001 for both). IUS showed higher specificity for bowel wall thickening, loss of wall stratification and stenosis (P=0.009, P<0.001 and P<0.001, respectively). Sensitivity and accuracy of IUS were higher in detecting ascites in active disease (P=0.002). Discussion Our results showed that IUS and MRE were equally accurate in detecting endoscopic activity. IUS may be the preferred technique for the evaluation of disease activity and for the follow-up of CD.