IMPORTANCE: Asian Indians are the fastest growing migration groups in the world. Studies evaluating the impact of migration on disease outcomes in this population are rare. BACKGROUND: We describe the methodology of the Singapore Indian Eye Study-2 (SINDI-2) aimed to evaluate the impact of migration status on diabetic retinopathy and other major age-related eye diseases in Asian Indians living in an urban environment. DESIGN: Population-based cohort study. PARTICIPANTS: A total of 2200 adults had participated in baseline SINDI (2007-2009, mean age [range] = 57.8 [42.7-84.1] years) and SINDI-2 (2013-2015, 56.5 [48.4-90.2] years). METHODS: Participants were classified as 'first generation' if they were Indian residents born outside of Singapore and as 'second-generation' immigrants (59.7% in SINDI vs. 63.6% in SINDI-2) if they were born in Singapore. MAIN OUTCOME MEASURES: Response rate, participant characteristics and prevalence of systemic diseases were stratified by migration status. RESULTS: Of the 2914 eligible SINDI participants invited to participate, 2200 participated in SINDI-2 (response rate of 75.2%). In both SINDI and SINDI-2, compared with first-generation immigrants, second-generation immigrants were younger, less likely to have income <1000 SGD, had lower levels of pulse pressure, higher levels of high-density lipoprotein cholesterol, had lower prevalence of hypertension and chronic kidney disease and had higher prevalence of current smoking and obesity (all P < 0.05). CONCLUSIONS AND RELEVANCE: In both SINDI and SINDI-2, second-generation immigrants had lower prevalence of cardiovascular risk factors except smoking and obesity compared with first-generation immigrants. The final report will confirm if these differences between generations are evident with regard to eye diseases.