Background: The main strategy for alleviating heart disease has been to target individuals and encourage them to change their health behaviors. Though important, emphasis on individuals has diverted focus and responsibility away from neighborhood characteristics, which also strongly influence people’s behaviors. Although a growing body of research has repeatedly demonstrated strong associations between neighborhood characteristics and cardiovascular health, it has typically focused on negative neighborhood characteristics. Only a few studies have examined the potential health enhancing effects of positive neighborhood characteristics, such as perceived neighborhood social cohesion. Methods: Using multiple logistic regression models, we tested whether higher perceived neighborhood social cohesion was associated with lower incidence of myocardial infarction. Prospective data from the Health and Retirement Study—a nationally representative panel study of American adults over the age of 50—were used to analyze 5,276 participants with no history of heart disease. Respondents were tracked for four years and analyses adjusted for relevant sociodemographic, behavioral, biological, and psychosocial factors. Results: In a model that adjusted for age, gender, race, marital status, education, and total wealth, each standard deviation increase in perceived neighborhood social cohesion was associated with a 22% reduced odds of myocardial infarction (OR = 0.78, 95% CI, 0.63-0.94. The association between perceived neighborhood social cohesion and myocardial infarction remained even after adjusting for behavioral, biological, and psychosocial covariates. Conclusions: Higher perceived neighborhood social cohesion may have a protective effect against myocardial infarction. What is already known on this subject? • Past research examining the associations between neighborhood-level factors and health, has largely focused on how negative neighborhood factors are associated with poorer health. • However, a growing body of research shows that positive neighborhood-level factors, such as neighborhood social cohesion, is associated with an array of positive outcomes including better: mental health, health behaviors, and physical health. What this study adds? • To our knowledge, this is the first study to prospectively examine the association between perceived neighborhood social cohesion and myocardial infarction. • Higher perceived neighborhood social cohesion was associated with lower myocardial infarction risk, even after adjusting for a wide range of covariates. • If future research replicates these findings, more neighborhood-level public health approaches that target neighborhood social cohesion may be warranted.