The goal of the study was to determine if there was an association between diet quality and cardiovascular risk factors (CVRF) in adults. NHANES 2001-2008 data were used to compare diet quality, as determined by using 2005 Healthy Eating Index (HEI-2005) scores, and CVRF in adults aged ≥19 y (n = 18,988; 51% men, 50% white, 21% African American, 25% Hispanic American, 4% other). HEI-2005 scores were calculated by using one 24-h dietary recall collected from the participants. Weight and adiposity, blood pressure, and CVRF were measured. Regression analyses were conducted to assess the linear relationship of CVRF and HEI-2005 scores by using appropriate covariates accounting for sample weights and the complex sample design of NHANES. OR were calculated for HEI quartiles and CVRF. BMI (P < 0.0001), waist circumference (WC) (P < 0.0001), diastolic blood pressure (P = 0.0002), C-reactive protein (P = 0.0016), total cholesterol (P = 0.0006), LDL cholesterol (P = 0.0039), and metabolic syndrome (P = 0.0035) were inversely associated with HEI-2005. HDL cholesterol significantly (P = 0.0048) increased across HEI-2005 quartiles. Compared with the lowest HEI-2005 quartile, individuals with the highest diet quality (HEI-2005 quartile 4) were less likely to be overweight or obese (34%) or have elevated WC (35%), elevated blood pressure (26%), metabolic syndrome (35%), and decreased HDL-cholesterol concentrations (21%). Data suggest that diet quality is inversely associated with several CVRF.