The level of fecal calprotectin (FC) can predict the onset of inflammatory bowel disease (IBD) with high accuracy and precision. We evaluated the cost-effectiveness of using measurements of FC to identify adults and children who require endoscopic confirmation of IBD. We constructed a decision analytic tree to compare the cost-effectiveness of measuring FC before endoscopy examination with that of direct endoscopic evaluation alone. A second decision analytic tree was constructed to evaluate the cost-effectiveness of FC cutoff levels of 100 μg/g vs 50 μg/g (typically used to screen for intestinal inflammation). The primary outcome measure was the incremental cost required to avoid 1 false-negative result by using FC level to diagnose new-onset IBD.In adults, FC screening saved $417/patient but delayed diagnosis for 2.2/32 patients with IBD among 100 screened patients. In children, FC screening saved $300/patient but delayed diagnosis for 4.8/61 patients with IBD among 100 screened patients. If endoscopic biopsy analysis remained the standard for diagnosis, direct endoscopic evaluation would cost an additional $18,955 in adults and $6250 in children to avoid 1 false-negative result from FC screening. Sensitivity analyses showed that cost-effectiveness of FC screening varied with the sensitivity of the test and the pre-test probability of IBD in adults and children. Pre-test probabilities for IBD of ≤75% in adults and ≤65% in children made FC screening cost-effective, but it was cost-ineffective if the probabilities were ≥85% and ≥78% in adults and children, respectively. Compared with the FC cutoff level of 100 μg/g, the cutoff level of 50 μg/g cost an additional $55 and $43 for adults and children, respectively, but it yielded 2.4 and 6.1 additional accurate diagnoses of IBD per 100 screened adults and children, respectively.Screening adults and children to measure fecal levels of calprotectin is effective and cost-effective in identifying those with IBD on a per-case basis when the pre-test probability is ≤75% for adults and ≤65% for children. The utility of the test is greater for adults than children. Increasing the FC cutoff level to ≥50 μg/g increases diagnostic accuracy without substantially increasing total cost.