Background: Repeat cross sectional surveys document the trend of prevalence rates for non-communicable diseases and their risk factors. In this study, we compare the prevalence rates for risk factors for cardiovascular disease in urban and rural Vellore between 1991–1994 and 2010–2012. Methods: Cross sectional survey was carried out in 1991–1994 in a rural block in Vellore district and in Vellore town, to study the prevalence of cardiovascular risk factors among adults aged 30–60 years. A repeat survey was done in 2010–2012 using the WHO STEPS method. In both surveys, socio-demographic and behavioral history, physical measurements, biochemical measurements, and medical history were obtained. Age adjusted rates were used to compare the rates in the two surveys. Results: In the rural areas, there was a three times increase in diabetes and body mass index (BMI) ≥25 kg/m2 (overweight/obese) with a doubling of the prevalence of hypertension. In urban areas there was a tripling of diabetes, doubling of proportion with BMI ≥ 25 kg/m2 and 50% increase in prevalence of hypertension. While the proportion of male current smokers reduced by 50% in both rural and urban Vellore, lifetime abstainers to alcohol decreased in the rural area from 46.8% to 37.5% (p < 0.001). Conclusions: There has been an alarming rise in diabetes, hypertension, and overweight/obese with an even greater increase in rural areas. Alcohol use is increasing while smoking is on the decline. Primary prevention programs are required urgently to stem the rising incidence of non-communicable diseases in India.