Introduction: Isolated terminal ileitis (ITI) is commonly found associated with Crohn’s disease but it has other etiologies too. Other common causes of ITI include nonsteroidal anti-inflammatory drug (NSAID) use, tuberculosis and other bacterial/parasitic infections, neoplasia, radiation or other autoimmune disorders. Methods: After obtaining IRB approval, a retrospective chart review was conducted on patients with biopsy proven ITI from May 2011 to May 2016 at our academic medical Centre. Data was collected pertaining to demographics, body mass index (BMI), associated Crohn’s disease or ulcerative colitis, treatment received and other causes of ileitis noted. Data was analyzed using SPSS software with chi square used to analyze categorical variables. P<0.05 was considered statistically significant. Results: A total of 229 patients with clinical symptoms and ITI on biopsy were reviewed. The mean age of our patients was 43.7 years old. Of the patient group, 49% (n=113/229) were males and the rest were females. Only 42% of patients with ITI were eventually diagnosed with Crohn's disease. Stool cultures were performed in 37% (n=86/229) of patients with positive results in 0.04% (n=4/86) of the patients. Most patients were treated with antibiotics after diagnosis of ileitis without determination of the exact etiology of the condition. Amongst those evaluated, one had tuberculosis, one had ischemic ileitis and one had Meckel’s diverticulum. NSAID use accounted for 26% (n=59/229) of ITI cases. Treatment generally involved antibiotics, initiation of biologics or use of 5-aminosalicylic acid products. The mean length of hospitalization was 1.25 days. Mean BMI of our patients was 25 kg/m2 and there was no statistically significant association noted between ITI and BMI. Presence of Crohn’s disease with ITI had a statistically significant association with positive clostridium difficile infection and subsequent need for treatment with biologics for isolated disease (p<0.001). Conclusions: Isolated terminal ileitis is commonly associated with Crohn’s disease but there are other conditions that should be suspected and can mimic Crohn’s disease histologically and endoscopically in the Ileum. NSAIDS are an important cause of ITI and need to be specifically inquired from the patient. If not considered it can result in misdiagnosis of Crohn’s disease and inappropriate treatment. Hence being aware of the wide range of differential diagnoses that can present with inflammation of the terminal ileum is important to avoid this inadvertent mislabeling. This retrospective study highlights the importance of other differentials when considering the management of a patient with ITI and not just focusing on only Crohn’s disease as the possible etiology.