Healing of mucosal lesions appears to offer significant benefit and is an important end point in clinical trials of treatment for Crohn's disease. The only validated endoscopic activity score at present is the Crohn's Disease Endoscopic Index of Severity, which is complicated and time consuming and, hence, is unsuitable for routine use. The aim of this study was to develop and to prospectively validate a simpler endoscopic score of disease activity, the Simple Endoscopic Score for Crohn's Disease. Selected endoscopic parameters (ulcer size, ulcerated and affected surfaces, stenosis) were scored from 0 to 3. Reproducibility for scoring of these parameters was evaluated through 71 examinations in which the endoscopist was paired with an observer. The simplest score (Simple Endoscopic Score for Crohn's Disease) that was highly correlated with both the Crohn's Disease Endoscopic Index of Severity and Crohn's Disease Activity Index was derived for 70 patients and then was prospectively validated in 121 different patients with Crohn's disease. The interobserver agreement for all selected endoscopic variables was excellent (kappa coefficient 0.791-1.000). Based on multiple linear regression, the Simple Endoscopic Score for Crohn's Disease resulted in the sum of the scores for ulcer size, ulcerated surface, affected surface, and luminal narrowing. In the validation phase of the study, a strong correlation was demonstrated for the Simple Endoscopic Score for Crohn's Disease with Crohn's Disease Endoscopic Index of Severity (r = 0.920). In addition, the Simple Endoscopic Score for Crohn's Disease was correlated to clinical parameters and serum C-reactive protein level. Simple Endoscopic Score for Crohn's Disease is a simple, reproducible, and easy-to-use endoscopic scoring system for Crohn's disease.