INTRODUCTION: Gastrointestinal subepithelial lesions are generally found incidentally during endoscopy or abdominal imaging, with an approximate prevalence of 0.4%. Our study aims at obtaining the Epidemiology of Sub-Epithelial Gastrointestinal lesions and factors influencing their Tissue yield by Endoscopic Ultrasound guided sampling in a predominantly African- American and Hispanic population. METHODS: In this retrospective observational study, we included the patients from a busy tertiary care County hospital, who underwent EUS from Jan 2010 through Jan 2018 for Sub-Epithelial Gastrointestinal lesions or found to have and SEL on EUS. Data was collected on basic demographic factors, EUS indications, finding, Histopathology and mode of final diagnosis. After collecting the data, we performed analysis with STATA 14.0 College Station, Texas. with Univariate and Multivariate Logistic Regression analysis for tissue sampling yield. RESULTS: 84 patients were included in our study of which 53% women 31% men. 18.6% of our population was uninsured and 41.4% were of African American ethnicity. Out of all the lesions majority were Gastric nodules [54.9%], 21.4% esophageal, 14.3% duodenal, 7.1 rectosigmoid and 1.2% periampullary. Of the total patients, 52.5% had some form of a tissue sampling [FNA, FNB, Forceps biopsy or EMR] and 47.6% had no biopsy. Of all the lesions seen in EUS, 41.7% were less than 1 cm nodules and 4.8% nodules measured >4cm. Echogenicity and the layer of lesion were also assessed. Univariate and Multivariate Logistic Regression to analyze the tissue sampling yield based on the above variables which showed that none of the variables had a statistically significant correlation to the tissue sampling yield, thus inferring that the yield may likely be dependent on the sampling method and the operator. CONCLUSION: Subepithelial lesions are those located beneath the epithelium and originate from any layer of the gastrointestinal wall.EUS is the best imaging modality to assess gastrointestinal subepithelial lesions and can be used for EUS guided tissue sampling, in addition to diagnostic sonological imaging of the nodule. It helps to distinguish extrinsic lesions from intramural ones based on the originating layer, echogenicity and tissue acquisition to reach an accurate diagnosis. In clinical practice, cytological and immunocytochemical results determine the final diagnosis. In contrary to other literature available, our study was done in a predominantly African American and Hispanic population.