Background A healthy diet, as defined by the US Dietary Guidelines for Americans (DGA), has been associated with lower morbidity and mortality from major chronic diseases in studies conducted in predominantly non-Hispanic white individuals. It is unknown whether this association can be extrapolated to African-Americans and low-income populations. Methods and Findings We examined the associations of adherence to the DGA with total and cause-specific mortality in the Southern Community Cohort Study, a prospective study that recruited 84,735 American adults, aged 40–79 y, from 12 southeastern US states during 2002–2009, mostly through community health centers that serve low-income populations. The present analysis included 50,434 African-Americans, 24,054 white individuals, and 3,084 individuals of other racial/ethnic groups, among whom 42,759 participants had an annual household income less than US$15,000. Usual dietary intakes were assessed using a validated food frequency questionnaire at baseline. Adherence to the DGA was measured by the Healthy Eating Index (HEI), 2010 and 2005 editions (HEI-2010 and HEI-2005, respectively). During a mean follow-up of 6.2 y, 6,906 deaths were identified, including 2,244 from cardiovascular disease, 1,794 from cancer, and 2,550 from other diseases. A higher HEI-2010 score was associated with lower risks of disease death, with adjusted hazard ratios (HRs) of 0.80 (95% CI, 0.73–0.86) for all-disease mortality, 0.81 (95% CI, 0.70–0.94) for cardiovascular disease mortality, 0.81 (95% CI, 0.69–0.95) for cancer mortality, and 0.77 (95% CI, 0.67–0.88) for other disease mortality, when comparing the highest quintile with the lowest (all p-values for trend < 0.05). Similar inverse associations between HEI-2010 score and mortality were observed regardless of sex, race, and income (all p-values for interaction > 0.50). Several component scores in the HEI-2010, including whole grains, dairy, seafood and plant proteins, and ratio of unsaturated to saturated fatty acids, showed significant inverse associations with total mortality. HEI-2005 score was also associated with lower disease mortality, with a HR of 0.86 (95% CI, 0.79–0.93) when comparing extreme quintiles. Given the observational study design, however, residual confounding cannot be completely ruled out. In addition, future studies are needed to evaluate the generalizability of these findings to African-Americans of other socioeconomic status. Conclusions Our results showed, to our knowledge for the first time, that adherence to the DGA was associated with lower total and cause-specific mortality in a low-income population, including a large proportion of African-Americans, living in the southeastern US., In a prospective cohort study, Wei Zheng and colleagues study the association between adherence to dietary guidelines and mortality in low-income US adults, two thirds of whom are African-Americans., Editors' Summary Background Certain parts of the population, including women, children, ethnic and racial minorities, and poor people, are often underrepresented in clinical trials and in epidemiological studies (which examine the patterns, causes, and effects of health and disease conditions). In the US population, the link between diet and health has mostly been studied in non-Hispanic white individuals from middle- and high-income households. Such studies formed the basis for the Dietary Guidelines for Americans (DGA), and more recently have shown that adherence to the DGA is associated with lower levels of obesity, as well as lower risks for diabetes, cardiovascular disease (such as heart attacks and strokes), and certain cancers. To measure adherence to the DGA, the Center for Nutrition Policy and Promotion at the US Department of Agriculture developed the Healthy Eating Index (HEI) in 1995. The DGA and the HEI have been updated several times, and the HEI-2010—the latest version—reflects the 2010 DGA. Why Was This Study Done? Because research participants are often not representative of the entire US population, it is unknown whether the results of many studies are valid for all Americans. To remedy this situation, efforts have been made to recruit participants from previously underrepresented parts of the population and to address important health questions in such groups. For this study, the researchers wanted to examine whether adherence to the DGA was associated with better health outcomes in poor people and African-Americans, consistent with the results in wealthier non-Hispanic white individuals. What Did the Researchers Do and Find? The researchers analyzed data from the Southern Community Cohort Study (SCCS). The SCCS was funded by the National Cancer Institute and was initiated in 2001 with the goal of addressing unresolved questions about the causes of cancer and other chronic diseases, as well as reasons for health disparities. The SCCS recruited most of its participants from community health centers in 12 states in the southeastern US. These centers serve predominantly poor and uninsured people, including many African-Americans. Of approximately 85,000 SCCS participants, over two-thirds were African-American, and over half were poor, with an annual household income of less than US$15,000. For this study, the researchers used a food frequency questionnaire that was designed to capture foods commonly consumed in the southeastern US, and from this calculated HEI-2010 scores for each participant. They also collected other health- and lifestyle-related information. They then followed all participants for whom they had complete information (over 77,000) for a number of years (half of them for over 6.2 years). During that period, 6,906 participants died; including 2,244 from cardiovascular disease, 1,794 from cancer, and 2,550 from other diseases. When the researchers tested for a possible association between HEI-2010 and death (controlling for other relevant factors such as age, weight, exercise, smoking, and the presence of specific chronic diseases), they found that participants with a higher HEI-2010 score (reflecting better adherence to the DGA) had a lower risk of dying in the follow-up period. Participants with the healthiest diet (those in the top one-fifth of HEI-2010 scores) had only about 80% of the risk of death of those with the unhealthiest diets (those in the bottom one-fifth of HEI-2010 scores). This reduction in the risk of death by approximately 20% was true for death from any disease, death from cancer, and death from cardiovascular disease. What Do These Findings Mean? The results support the validity of the DGA for healthy eating across the US population. However, the study had some limitations. For example, participants were asked only once—when they first joined the SCCS—about their diet, their household income, and other factors that can change over time, such as exercise habits and diseases they have been diagnosed with. Besides such changes, there could be other factors not captured in the study that might influence the association between diet and death. Despite these uncertainties, the findings suggest that adherence to the DGA is associated with lower total mortality and mortality from cancer or cardiovascular disease in poor US Americans in general, and in low-income African-Americans. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001830. Information is available online about the Southern Community Cohort Study The US Department of Agriculture’s Center for Nutrition Policy and Promotion has information on the Healthy Eating Index, which is based on the Dietary Guidelines for Americans The World Health Organization provides information on diet as part of its global strategy for diet, physical activity, and health, as well as a factsheet on healthy diet Wikipedia has a page on race and health in the US (note that Wikipedia is a free online encyclopedia that anyone can edit)