Background: Inflammatory bowel diseases (IBD) are organic chronic inflammation of the gastrointestinal tract characterized by variable disease activity with repeated periods of remission and exacerbation. Irritable bowel syndrome (IBS) is prevalent in up to fifth of population; diarrhea type has the broadest differential diagnosis. To distinguish inflammatory versus functional disorder fecal biomarkers as fecal lactoferrin (FL), being non-invasive acute phase proteins produced by inflamed mucosa, can help to avoid invasive procedures. Objective: The aim of this study was to assess sensitivity and specificity of fecal lactoferrin as a non-invasive biomarker in Egyptian patients with IBD and to detect its role in assessment of disease severity. Patients and methods: This comparative case control study was held through one year duration. Patients were recruited from Internal Medicine and Hepatology Department at a University Hospital. 50 subjects were classified into 3 groups: Group I included 30 patients with inflammatory bowel disease, Group II included 10 patients with irritable bowel syndrome, Group III included 10 healthy subjects as control group. Results: fecal lactoferrin assay (FLA) levels were highest in patients with IBD in comparison with IBS patients and healthy group. Moreover FLA levels also correlated significantly with disease severity in patients with IBD as higher levels of FLA were found in patients with severe ulcerative colitis (UC) or Crohn`s disease. Conclusion: Fecal lactoferrin can be used to differentiate IBD from IBS with 96.7% sensitivity and 100% specificity at cutoff value of 37 ug/ml while at cutoff value 7.2 ug/ml FLA has 100% sensitivity and specificity in differentiating IBD patients from healthy subjects in Egyptian population. Yet it can't differentiate ulcerative colitis versus Crohn's disease.