BACKGROUND AND AIMS: The Crohn's Disease Activity Index (CDAI) has been criticised due to heavy weighting on subjective clinical symptoms. C-reactive protein (CRP) and endoscopic lesions are objective measures of inflammation. We investigated the relationships between clinical disease activity, CRP normalisation and mucosal healing in Crohn's disease (CD). METHODS: The Study of Biologic and Immunomodulator Naive Patients in CD trial compared infliximab to azathioprine and to infliximab plus azathioprine in 508 CD patients. Mucosal healing was defined as the absence of mucosal ulceration at the week 26 ileocolonoscopy in a patient who had evidence of ulceration at the baseline ileocolonoscopy. RESULTS: 188 patients who had evaluable ileocolonoscopy with evidence of mucosal ulceration at baseline, CDAI scores and CRP values at baseline and week 26 were analysed. Seventy-two of 136 patients (53%) who had a CDAI<150 at week 26 achieved mucosal healing, and 38 of 90 patients (42%) achieved both CRP normalisation (CRP<0.8 mg/dL) and mucosal healing while in clinical remission. The positive predictive value (PPV) and negative predictive value (NPV) of CDAI to detect mucosal healing using 150 as a cut-off for CDAI were 65% and 53%, respectively. The PPV and NPV of CDAI to detect mucosal healing and CRP normalisation using 150 as a cut-off for CDAI were 79% and 42%, respectively. CONCLUSIONS: Half the patients under azathioprine and/or infliximab in clinical remission have endoscopic and/or CRP evidence of residual active CD, whereas other patients with endoscopic and CRP normalisation have persistent clinical symptoms. Clinical symptoms as scored by CDAI are not a reliable measure of the underlying inflammation.