BACKGROUND AND AIMS: Crohn's disease (CD) has emerged as a global disease, with the fastest rise in incidence in Asia. The impact of immigration (reflecting early life exposure to one environment, and later life to another) on disease phenotype, behavior, and seropositivity has not been examined previously. METHODS: We phenotyped a cohort of US-residing (immigrant) SA-CD patients and controls from 3 US-hospitals compared to native SA-CD patients and controls from India and Singapore. These cohorts were compared to a prospective cohort of 1679 US white-CD patients. Detailed disease phenotype, treatment, acculturation, environmental exposures and serologies were ascertained. RESULTS: Our study consisted of 260 immigrant SA-CD patients and controls, 198 native SA-CD patients and controls, and 1679 US White-CD patients. Both native (59%, p=0.02) and immigrant (55%, p=0.15) SA-CD demonstrated male predominance compared to White-CD patients (49%). The mean age at diagnosis for 2(nd)-generation immigrants (17.7 years) was significantly lower than 1(st)-generation immigrants (34 years), native SA-CD(31.7 years) and white-CD (27.7 years); the age at diagnosis was also younger in Western/bicultural identifying compared to Asian-identifying immigrants(p<0.05). Second-generation CD patients were more likely to have B1 disease compared to native and 1(st)-generation SA-CD(OR 3.48, p=0.007). Immigrant-CD patients had higher frequency of perianal involvement compared to native SA-CD and White-CD. However, native-CD patients more commonly had stricturing disease. Immigrant SA-CD cohort had higher anti-cbir1(49%), anti-OmpC positivity rates (19%) than ASCA(13%). CONCLUSION: Our international, multicenter study identified both commonalities as well as unique differences in disease phenotype, behavior, serological patterns and environmental factors by geography and immigrant status. We highlight the importance of changing environment on CD phenotypic expression.