The Framingham Heart Study is a long-term, ongoing cardiovascular cohort study of residents of the city of Framingham, Massachusetts. The study began in 1948 with 5,209 adult subjects from Framingham, and is now on its third generation of participants. Prior to the study almost nothing was known about the epidemiology of hypertensive or arteriosclerotic cardiovascular disease. Much of the now-common knowledge concerning heart disease, such as the effects of diet, exercise, and common medications such as aspirin, is based on this longitudinal study. It is a project of the National Heart, Lung, and Blood Institute, in collaboration with (since 1971) Boston University. Various health professionals from the hospitals and universities of Greater Boston staff the project.

In 1948, the study was commissioned by the United States Congress, with multiple communities being considered for study. The final choice was between Framingham, Massachusetts, and Paintsville, Kentucky. Framingham was chosen when residents showed more general interest in heart research than Paintsville. Thomas Royle Dawber was director of the study from 1949 to 1966. He was appointed as chief epidemiologist shortly after the start of the project, when it was not progressing well. The study had been intended to last 20 years; however, interest grew in part due to Dr. Dawber's efforts to promote the study and engage in fundraising after he had been transferred to Boston to accept a chairmanship of preventive medicine. By 1968, it was debated whether the original study had served its purpose and should be terminated as scheduled. A committee gathered and considered that, after 20 years of research, the Framingham study should come to an end, since their hypothesis had been tested and extensive information concerning heart diseases had been gathered. Despite this conclusion, Congress failed to accept the recommendation, instead voting to continue the study. The study has been split into different segments, or "cohorts".^{[citation needed]}

William P. Castelli is a former director of the Framingham Heart Study.

Over 3,000 peer-reviewed scientific papers have been published related to the Framingham Heart Study. It is generally accepted that the work is outstanding in its scope and duration, and overall is considered very useful.^{[citation needed]}

It was rightly assumed from the start of the Framingham Heart Study that cardiac health can be influenced by lifestyle and environmental factors, and by inheritance. The Framingham Heart Study is the source of the term risk factor. Before the Framingham Heart Study, doctors had little sense of heart disease prevention. In the 1950s, it was believed that clogging of arteries and narrowing of arteries (atherosclerosis, arteriosclerosis) were normal parts of aging, and that they occurred universally as people became older. High blood pressure (hypertension) and elevated serum cholesterol (hypercholesterolemia) were also seen as normal consequences of aging in the 1950s, and no treatment was available. These and further risk factors, such as homocysteine, were gradually discovered over the years.

The Framingham Heart Study, along with other important large studies, such as the Seven Countries Study and the Nurses' Health Study, also showed that healthy diet, not being overweight or obese, and regular exercise are all important in maintaining good health, and that there are differences in cardiovascular risk between men and women. Along with other important studies about smoking, such as the British Doctors Study, it also confirmed that cigarette smoking is a highly significant factor in the development of heart disease, leading in many cases to angina pectoris, myocardial infarction (MI), and coronary death.

Recently the Framingham studies have come to be regarded as overestimating risk, particularly in the lower risk groups, such as for UK populations.

One question in evidence-based medicine is how closely the people in a study resemble the patient with whom the health care professional is dealing.