SummaryBackgroundSymptoms of inflammatory bowel disease (IBD) often overlap with those of irritable bowel syndrome (IBS).AimTo evaluate the diagnostic performance of faecal calprotectin in distinguishing patients with IBD from those with IBSMethodsWe searched MEDLINE, Embase, Scopus, and Cochrane Library databases up to 1 January 2023. Studies were included if they assessed the diagnostic performance of faecal calprotectin in distinguishing IBD from IBS (defined according to the Rome criteria) using colonoscopy with histology or radiology as reference standard in adults. We calculated summary sensitivity and specificity and their 95% confidence intervals (CI) using a random‐effect bivariate model. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies II.ResultsWe included 17 studies with a total of 1956 patients. The summary sensitivity was 85.8% (95% CI: 78.3–91), and the specificity was 91.7% (95% CI: 84.5–95.7). At a prevalence of IBD of 1%, the negative predictive value was 99.8%, while the positive predictive value was only 9%. Subgroup analyses showed a higher sensitivity in Western than in Eastern countries (88% vs 73%) and at a cut‐off of ≤50 μg/g than at >50 μg/g (87% vs. 79%), with similar estimates of specificity. All studies were at “high” or “unclear” risk of bias.ConclusionsFaecal calprotectin is a reliable test in distinguishing patients with IBD from those with IBS. Faecal calprotectin seems to have a better sensitivity in Western countries and at a cut‐off of ≤50 μg/g.