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Background: South Asians have recently been identified as having a rapidly rising incidence and prevalence of inflammatory bowel disease (IBD) throughout the world. However, longitudinal phenotypic studies of South Asians living in the United States remain scarce., Methods: We retrospectively studied 171 South Asian patients with IBD treated at 2 US tertiary centers who presented between 2000 and 2016. South Asian IBD patients were randomly matched in a 1:2 ratio with sex and IBD subtype-matched (ulcerative colitis [UC] vs Crohn disease [CD]) white control patients (n = 342). Demographic and phenotypic characteristics were evaluated and compared between the 2 groups. Odds ratios (OR), logistic regression, and survival analysis were performed using R studio and STATA., Results: 81 South Asian patients and 162 white patients had CD, and 90 South Asians and 180 white patients had UC. Among the CD group, South Asian patients were diagnosed at a median older age (age 28) than white patients (21 years; P < 0.003). Fistulizing disease (24.1% vs 8.6%; P < 0.002), perianal disease (20.3% vs 2.5%; P < 0.005), and presentation of rectal pain (16.2% vs 2.9%; P < 0.001) were more common among South Asian patients with CD than among white patients. After adjusting for covariates, South Asian patients with CD were less likely to be placed on thiopurines (OR = 0.36; P < 0.007) or to receive more than 1 biologic (OR = 0.42; P < 0.040). South Asian patients with UC were less likely to have proctitis (10% vs 22.2%; P < 0.022) and more likely to have primary sclerosing cholangitis (n = 7 vs n = 2; P < 0.007). South Asian patients born in the United States or those who had migrated before age 5 were younger at the age of IBD diagnosis (age 18.9 vs 32.4; P < 0.0005)., Conclusion: We found unique demographic and phenotypic characteristics among South Asian patients, including more penetrating disease in those with CD and less proctitis among those with UC, along with altered medication use patterns. Distinct environmental exposures and a potentially unique genetic profile of South Asian patients may confer this variable phenotypic expression, influencing management of this increasingly at-risk population., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)