ABSTRACT Healthy dietary habits are the cornerstone of cardiovascular disease (CVD) prevention. Numerous researchers have developed diet quality indices to help evaluate and compare diet quality across and within various populations. The availability of these new indices raises questions regarding the best selection relevant to a given population. In this perspective, we critically evaluate a priori–defined dietary indices commonly applied in epidemiological studies of CVD risk and mortality. A systematic literature search identified 59 observational studies that applied a priori–defined diet quality indices to CVD risk factors and/or CVD incidence and/or CVD mortality. Among 31 different indices, these scores were categorized as follows: 1) those based on country-specific dietary patterns, 2) those adapted from distinct dietary guidelines, and 3) novel scores specific to key diet-related factors associated with CVD risk. The strengths and limitations of these indices are described according to index components, calculation methods, and the application of these indices to different population groups. Also, the importance of identifying methodological challenges faced by researchers when applying an index are considered, such as selection and weighting of food groups within a score, since food groups are not necessarily equivalent in their associations with CVD. The lack of absolute cutoff values, emphasis on increasing healthy food without limiting unhealthy food intake, and absence of validation of scores with biomarkers or other objective diet assessment methods further complicate decisions regarding the best indices to use. Future research should address these limitations, consider cross-cultural and other differences between population groups, and identify translational challenges inherent in attempting to apply a relevant diet quality index for use in CVD prevention at a population level.