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Nearly 70% of adult Americans are overweight or obese, but the associations between physical activity, diet quality, and weight status have not been examined in a representative sample of US adults. The purpose of this study was to examine the associations among moderate-to-vigorous physical activity (MVPA), diet quality, and weight status within and across age groups in US adults.Participants included 2587 men and 2412 women age 20 to ≥70 yr from the National Health and Nutrition Examination Survey 2003–2004 and 2005–2006. Physical activity was measured by accelerometry. Diet quality was assessed with overall Healthy Eating Index-2005 scores. Measures of weight status, body mass index (BMI), and waist circumference were assessed using standard National Health and Nutrition Examination Survey protocols.Across age groups, MVPA was lower in the older age groups for both men and women, whereas diet quality was higher (P < 0.001). BMI and waist circumference were also higher in the older age groups (P < 0.05). Within age groups, MVPA was inversely associated with BMI and waist circumference for men and women in nearly every age group (P < 0.05). Diet quality was inversely associated with the weight status variables only in men age 30–39, 40–49 (BMI only), and 50–59 yr and women age 50–59 yr (P < 0.05).We observed clear age-related trends for measures of weight status, physical activity, and diet quality in US men and women. MVPA was very consistently related to weight status in both genders. The relation between diet quality and weight status was less consistent. These findings provide support for public health efforts to prevent obesity by promoting increased physical activity in adult Americans.