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Background: The demographic transition in South Asia coupled with unplanned urbanization and lifestyle changes are increasing the burden of non-communicable disease (NCD) where infectious diseases are still highly prevalent. The true magnitude and impact of this double burden of disease, although predicted to be immense, is largely unknown due to the absence of recent, population-based longitudinal data. The present study was designed as a unique ‘Framingham-like’ Pakistan cohort with the objective of measuring the prevalence and risk factors for hypertension, obesity, diabetes, coronary artery disease and hepatitis B and C infection in a multi-ethnic, middle to low income population of Karachi, Pakistan. Methods: We selected two administrative areas from a private charitable hospital’s catchment population for enrolment of a random selection of cohort households in Karachi, Pakistan. A baseline survey measured the prevalence and risk factors for hypertension, obesity, diabetes, coronary artery disease and hepatitis B and C infection. Results: Six hundred and sixty-seven households were enrolled between March 2010 and August 2011. A majority of households lived in permanent structures (85%) with access to basic utilities (77%) and sanitation facilities (98%) but limited access to clean drinking water (68%). Households had high ownership of communication technologies in the form of cable television (69%) and mobile phones (83%). Risk factors for NCD, such as tobacco use (45%), overweight (20%), abdominal obesity (53%), hypertension (18%), diabetes (8%) and pre-diabetes (40%) were high. At the same time, infectious diseases such as hepatitis B (24%) and hepatitis C (8%) were prevalent in this population. Conclusion: Our findings highlight the need to monitor risk factors and disease trends through longitudinal research in high-burden transition communities in the context of rapid urbanization and changing lifestyles. They also demonstrate the urgency of public health intervention programs tailored for these transition communities. [ABSTRACT FROM AUTHOR]