Background: Little is known about the long-term health consequences of following the 2005 Dietary Guidelines for Americans (DGA; Washington, DC: US Government Printing Office, 2005). Objective: The objective was to examine the longitudinal association between diets consistent with the 2005 DGA and subsequent weight gain. Design: We used data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a cohort of black and white men and women aged 18-30 y at baseline who attended ≤7 examinations from 1985-1986 to 2005-2006 (n = 4913). We created a 100-point Diet Quality Index (2005 DQI) to rate participants' diets based on meeting the 2005 DGA key recommendations. Longitudinal models of weight gain were adjusted for physical activity, smoking, energy intake, age, education, sex, and initial body mass index (BMI) and included interaction terms of DQI by race and initial BMI (if statistically significant). Results: We found effect modification by race (likelihood ratio test, P < 0.03 in all models). The mean adjusted 20-y weight change was +19.4 kg for blacks and +11.2 kg for whites with high diet quality (DQI >70) and +17.8 for blacks and +13.9 for whites with a DQI <50 (P < 0.05). In race-specific Cox models (with interaction terms for DQI x initial BMI, P < 0.05), a 10-point increase in DQI score was associated with a 10% lower risk of gaining 10 kg in whites with an initial BMI (in kg/m2) ,25 but with a 15% higher risk in blacks with baseline obesity (P < 0.001). Conclusions: Our findings do not support the hypothesis that a diet consistent with the 2005 DGA benefits long-term weight maintenance in American young adults. Greater need for attention to obesity prevention in future DGAs is warranted.