Coronary heart disease (CHD) is a major cause of morbidity, disability, mortality, and health expenditures worldwide. A wealth of studies has demonstrated that people of South Asian ancestry have a higher risk of CHD and particularly premature CHD than most other racial/ethnic groups, and recent research suggests that this risk is higher in Pakistanis than in Indians-the two largest SA groups. Pakistan is the 5th most populous country in the world, and despite these concerning trends, so far there has been a scarcity of large studies evaluating the prevalence of cardiovascular risk factors and subclinical coronary atherosclerosis in young-to-middle-aged Pakistanis. Also, there is currently no cardiovascular risk score specifically tailored to younger Pakistani men and women. The PAKistan Study of prEmature coronary atHerosclerosis in young AdulTs (PAK-SEHAT) aims at addressing these important gaps. PAK-SEHAT is an ongoing prospective cohort study that will enroll 2,000 asymptomatic Pakistani men aged 35 to 60 years and women aged 35 to 65 years from the general population, free of clinically overt cardiovascular disease. Participants will undergo a comprehensive baseline exam including coronary computed tomography angiography, and will be followed for incident events and repeat testing for 5 years. PAK-SEHAT will allow determining the prevalence, severity, determinants, and prognostic significance of early atherosclerosis in apparently healthy young-to-middle-aged Pakistanis. This knowledge can help inform primordial and primary prevention strategies, enhanced cardiovascular risk stratification, and potential plaque-screening approaches in Pakistan, all of which can ultimately help reduce the burden of CHD in the country. In this report investigators describe the rationale, objectives, methods, and discuss the potential implications of the PAK-SEHAT study.