BACKGROUND: Fecal calprotectin is a marker of inflammation in inflammatory bowel disease (IBD). Since mucosal healing has become a goal of treatment in IBD we examined how reliably calprotectin levels reflect mucosal disease activity. METHODS: In all, 126 IBD patients and 32 irritable bowel syndrome (IBS) patients needing colonoscopy delivered a sample of feces prior to the start of bowel cleansing. Besides collection of symptom scores and blood tests, experienced endoscopists recorded the Simple Endoscopic Score for Crohn's Disease (SES-CD) and the Crohn's Disease Endoscopic Index of Severity (CDEIS) in Crohn's disease (CD) patients and the Mayo endoscopic score in ulcerative colitis (UC) patients. Stool samples were shipped for central calprotectin PhiCal Assay (enzyme-linked immunosorbent assay [ELISA]). Correlation analysis was done with Pearson statistics. RESULTS: The median (interquartile range [IQR]) fecal calprotectin levels were 175 (44-938) μg/g in CD, 465 (61-1128) μg/g in UC, and 54 (16-139) μg/g in IBS. Correlations were significant with endoscopic disease scores in both CD and in UC. Using ROC statistics, a cutoff value of 250 μg/g indicated the presence of large ulcers with a sensitivity of 60.4% and a specificity of 79.5% (positive predictive value [PPV] 78.4%, negative predictive value [NPV] 62.0%) in CD. Levels ≤250 μg/g predicted endoscopic remission (CDEIS ≤3) with 94.1% sensitivity and 62.2% specificity (PPV 48.5%, NPV 96.6%). In UC, a fecal calprotectin >250 μg/g gave a sensitivity of 71.0% and a specificity of 100.0% (PPV 100.0%, NPV 47.1%) for active mucosal disease activity (Mayo >0). Calprotectin levels significantly correlated with symptom scores in UC (r = 0.561, P < 0.001), but not in CD. CONCLUSIONS: Fecal calprotectin levels correlate significantly with endoscopic disease activity in IBD. The test appears useful in clinical practice for assessment of endoscopic activity and remission. (Inflamm Bowel Dis 2012;).