BACKGROUND: The endoscopic substudy of the ACCENT I (A Crohn's Disease Clinical Trial Evaluating Infliximab in a New Long-term Treatment Regimen) Crohn's disease trial examined the effects of infliximab on mucosal inflammation and mucosal healing, and assessed their impact on outcomes. DESIGN: ACCENT I was a randomized, double-blind, parallel group study. SETTING: This study took place at multiple centers in North America, Europe, and Israel. MAIN OUTCOME MEASUREMENTS: Ileocolonoscopic examinations were performed at weeks 0, 10, and 54. Complete mucosal healing was defined as the absence of all mucosal ulcerations. The end point of principal interest was the proportion of patients randomized as responders with mucosal healing at week 10. The proportion of responders who demonstrated mucosal healing at week 54 or at both weeks 10 and 54 is also summarized. Changes in Crohn's disease endoscopic index of severity (CDEIS) scores from baseline to week 10 and 54 were calculated for all patients in this substudy. RESULTS: Complete mucosal healing by week 10 occurred in significantly more week 2 responders who had received 3 doses of infliximab compared with a single dose (31% vs. 0%, p = 0.010). A significantly higher proportion of week 2 responders in the combined scheduled maintenance group had complete mucosal healing at week 54 compared with the episodic group (50% vs. 7%, p = 0.007). The results for all patients are consistent with those for week 2 responders only. Significantly greater improvement in the CDEIS occurred with scheduled maintenance compared with episodic treatment at week 10 (p </= 0.001) and week 54 (p = 0.026). Notably, no strong relationship between clinical remission and complete mucosal healing was found. Overall, mucosal healing appeared to correlate with fewer hospitalizations, although these results were not statistically significant. CONCLUSIONS: Scheduled infliximab maintenance therapy resulted in more improvement in mucosal ulceration and in higher rates of mucosal healing. There was a numerical trend for patients with better mucosal healing to have a lower rate of Crohn's disease-related hospitalizations.