Aim To evaluate the performance of Madras Diabetes Research Foundation -Indian Diabetes Risk Score (MDRF-IDRS score) in different ethnic groups including Indians, Hispanic, Non-Hispanic Whites, Non-Hispanic Blacks and other American. Methods The MDRF-IDRS score is calculated based on a risk equation that includes age, waist circumference, family history of diabetes and physical activity. The National Health and Nutrition Examination Survey (NHANES) data on American and Chennai Urban Rural Epidemiology Study data on Indians were used in this study. Study participants aged ≥ 20 years with and without type 2 diabetes were included. Performance of the MDRF-IDRS score was assessed using sensitivity, specificity, positive predictive value, negative predictive value and the area under the receiver operating characteristic curve measures within each ethnic group. IDRS scores' performance was then compared with existing non-invasive American diabetes risk scores. Results Total number of participants included was 11,035 (2292 Indians and 8743 American). MDRF-IDRS score (cut off≥ 60) performed well in Indians with an AUC, sensitivity and specificity of 0.73, 80.2% and 57.3% respectively. MDRF-IDRS score cut off ≥ 70 had the highest discriminative performance among Hispanic, Non-Hispanic Whites and Non-Hispanic Blacks with sensitivity and specificity of between 70.1-86.9% and 61.2-72.2% respectively. The AUC for American was between 0.77-0.81 with the highest and lowest AUC in Non-Hispanic Black and Non-Hispanic White respectively. With a smaller number of variables, IDRS score showed almost the same performance in predicting diabetes among American compared with the existing non-invasive American diabetes risk score. Conclusion The MDRF-IDRS score performs well among Indians and American including Hispanic, Non-Hispanic White, Non-Hispanic Black and other American. It can be used as a screening tool to help in early diagnosis, management and optimal control of diabetes mainly in mass screening programmes in India and America