BACKGROUND AND AIMS: Fecal calprotectin (FC) is a noninvasive biomarker used in inflammatory bowel disease (IBD) management and risk stratification of nonspecific gastrointestinal symptoms. Leukocyte esterase is an inexpensive and widely available point-of-care inflammatory marker present on urinalysis test strips. We aim to assess the diagnostic accuracy of fecal leukocyte esterase (FLE) relative to FC and endoscopy and demonstrate its use as an alternative biomarker for IBD. METHODS: In this prospective cohort study, 70 patients who had FC ordered as part of standard clinical care also received FLE testing. FLE levels were compared with various FC cutoff values and endoscopy and pathology findings as the gold standard. RESULTS: As the FC cutoff increased from 50 to 500 mg/g, FLE sensitivity increased from 67% to 95% while the specificity decreased from 86% to 76%. The area under the receiver operating characteristic (AUROC) curve increased from 0.79 to 0.90. An FLE of 1þ had the best test characteristics. Among patients who underwent endoscopic evaluation, FLE demonstrated an identical sensitivity (75%) and specificity (86%) to FC in predicting endoscopic inflammation. AUROC was 0.80 for FLE and 0.85 for FC with an optimal cutoff of 2þ and 301 mg/g, respectively. When used to distinguish between patients with active IBD and no/inactive IBD, FLE had a sensitivity of 84% and specificity of 90%, comparable with the 84% and 83%, respectively, of FC. AUROC was 0.88 for FLE and 0.91 for FC with an optimal cutoff of 2þ and 145 mg/g, respectively. CONCLUSION: FLE demonstrates adequate correlation and comparable accuracy with FC in predicting endoscopic inflammation and distinguishing between patients with active vs inactive IBD.