Background: The Healthy Eating Index (HEI) is a measure of diet quality developed based on the Dietary Guidelines for Americans (DGA). Objective: The objective was to assess the diet quality of a multiethnic population using and comparing the 2 HEIs, the updated HEI (HEI-05) based on the 2005 DGA and the original 1990 HEI (HEI-90), with the objective of predicting obesity outcomes. Design: A longitudinal analysis of survey and clinical data from 6236 middle-aged and elderly white, African American, Hispanic, and Chinese participants of the Multi-Ethnic Study of Atherosclerosis (MESA) was conducted. Baseline diet quality was assessed with the use of HEI-90 and HEI-05. Baseline and 18-mo follow-up body mass index (BMI) and waist circumference (WC) data were predicted by using z score multiple regression models, and categorical obesity status was predicted by using multinomial logistic regression. Results: Overall, the HEI-05 had larger z score β coefficients than did the HEI-90 (eg, in whites, -0.53 compared with -0.48 in baseline BMI, -0.54 compared with -0.47 in follow-up BMI, -1.67 compared with -1.56 in baseline WC, and -1.57 compared with -1.44 in follow-up WC). Among whites only, both HEIs were significant predictors of BMI and WC (all P < 0.001). The odds of being obese rather than normal weight were inversely related to HEI z scores primarily in whites (P < 0.05). Conclusions: The changes to the 2005 DGA, as reflected by HEI-05, appear to better predict obesity outcomes in this multi-ethnic population, primarily in whites. Additional research on ethnic-specific DGA adherence and its relation to health outcomes is needed.