To examine the relationships among dietary quality, weight status, and human immunodeficiency virus (HIV) infection in US adolescents and young adults. This cross-sectional study was embedded in the Reaching for Excellence in Adolescent Care and Health cohort study of HIV-infected and HIV-uninfected, at-risk youth. Biochemical, clinical, and sociodemographic data were available. Dietary intake was collected using the Block Food Frequency Questionnaire and a modified Healthy Eating Index was calculated to measure diet quality. Participants included 264 HIV-infected and 127 HIV-uninfected youth 13 to 23 years old (75.2% women, 67.3% African American/non-Hispanic, 20.5% Hispanic, 12.3% other) at 14 clinic sites. Determinants of obesity and the modified Healthy Eating Index were tested using logistic and generalized linear regression. About half (51.7%) of participants were overweight or obese. Obesity was positively associated with being a woman, living independently, watching television ≥3 hours per day, previous dieting, and being from the northeastern or southern United States. Youth who were HIV uninfected or HIV infected with CD4 + T cells ≥500 cells/μL had similar obesity rates; overweight (25%) and obesity (20%) was prevalent among women even with CD4 + T cells <200 cells/μL. The modified Healthy Eating Index score was 56.2±0.6, reflecting a diet needing improvement. HIV infection, watching television ≥3 hours/day, and being from the Chicago, IL, area were associated with a lower-quality diet. Obesity is a common nutrition problem for both HIV-infected and uninfected youth; however, HIV-infected youth are at increased risk of developing metabolic abnormalities. Culturally appropriate, client-focused nutrition education will help youth improve their diet and increase physical activity to reduce health consequences associated with both obesity and HIV infection.