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Aim: To evaluate the utility of fecal calprotectin (FC) in predicting relapse and endoscopic activity during follow-up in an inflammatory bowel disease (IBD) cohort., Methods: All FC measurements that were obtained during a 3-year period from patients with inflammatory bowel disease in clinical remission were identified. Data regarding the short-term (6 mo) course of the disease were extracted from the medical files. Exclusion criteria were defined as: (1) An established flare of the disease at the time of FC measurement, (2) Loss to follow up within 6 mo from baseline FC measurement, and, (3) Insufficient data on file. Statistical analysis was performed to evaluate whether baseline FC measurement could predict the short term clinical relapse and/or the presence of mucosal healing., Results: We included 149 [Crohn's disease (CD) = 113, Ulcerative colitis (UC) = 36, male = 77] IBD patients in our study. Within the determined 6-month period post-FC measurement, 47 (31.5%) had a disease flare. Among 76 patients who underwent endoscopy, 39 (51.3%) had mucosal healing. Baseline FC concentrations were significantly higher in those who had clinical relapse compared to those who remained in remission during follow up (481.0 μg/g, 286.0-600.0 vs 89.0, 36.0-180.8, P < 0.001). The significant predictive value of baseline median with IQR FC for clinical relapse was confirmed by multivariate Cox analysis [HR for 100μg/g: 1.75 (95%CI: 1.28-2.39), P = 0.001]. Furthermore, lower FC baseline values significantly correlated to the presence of mucosal healing in endoscopy (69.0 μg/g, 30.0-128.0 vs 481.0, 278.0-600.0, in those with mucosal inflammation, median with IQR, P < 0.001). We were able to extract cut-off values for FC concentration with a high sensitivity and specificity for predicting clinical relapse (261 μg/g with AUC = 0.901, sensitivity 87.2%, specificity 85.3%, P < 0.001) or mucosal healing (174 μg/g with AUC = 0.956, sensitivity 91.9%, specificity 87.2%, P < 0.001). FC was better than CRP in predicting either outcome; nevertheless, having a pathological CRP (> 5 mg/L) in addition to the cut-offs for FC, significantly enhanced the specificity for predicting clinical relapse (95.1% from 85.3%) or endoscopic activity (100% from 87.2%)., Conclusion: Serial FC measurements may be useful in monitoring IBD patients in remission, as FC appears to be a reliable predictor of short-term relapse and endoscopic activity., Competing Interests: Conflict-of-interest statement: The authors have no conflict of interest to declare.