This study compared difference in diabetes, obesity, metabolic syndrome (MetS), C-reactive protein (hs-CRP), homocysteine, and other cardiovascular risk factors between rural and urban Asian Indians using similar/standardized field measurements. The design used a cross-sectional and population-based study among rural (Tamil Nadu) and urban (Delhi) Asian Indians aged 18 years and older. 574 rural Indians and 508 urban Indians completed face-to-face interviews, and anthropometric measurements. Fasting venous blood samples were obtained for fasting plasma glucose and serum lipid tests. The mean age was 42.6±11.8 y (urban) and 39.5±13.9 y (rural). Although the prevalence of type 2 diabetes (T2DM) was lower in rural (8.4%) than urban (13.6%) areas, rural Asian Indians had a higher percent of undiagnosed cases (25%), poorer glycemic control, and unawareness of diabetes than their urban peers. Urban Indians had elevated rates of the MetS (as defined by NCEP and IDF criteria), hs-CRP, total cholesterol, LDL, and hypertension than their rural peers. Females in general had significantly higher central obesity and lower HDL-C than males. Homocysteine levels (measured only among urban respondents) was higher among males than females (p=.04). Prevalence of hypertension increased with age (r=.37, p<.001) and correlated with respondents' blood glucose levels (r=.11, p<.001). There was a step-wise worsening of risk factors as individuals progressed from normal to IFG to T2DM. High burden of diabetes and other cardiovascular risk factors in urban and rural Asian Indians provide basis for tailored and cost-effective prevention and intervention programs, in such resource-constrained settings.