Abstract Purpose Dietary patterns differ by day of the week. This study examined weekend-weekday differences in diet among U.S. adults. Methods Nationally representative data of 11,646 adults 18 years of age and above from the National Health and Nutrition Examination Survey 2003–2012 waves were analyzed. Individual fixed-effect regressions were performed using data from two nonconsecutive 24-hour dietary recalls. Results Weekend diet was less healthful than weekday, with diet on Saturday the worst. Compared with weekday consumption, consumption on Saturday was associated with an increase in daily intakes of total energy by 181.04 kcal, energy from sugar-sweetened beverages 18.34 kcal, energy from alcohol 46.65 kcal, energy from discretionary foods 48.77 kcal, total fat 8.16 g, saturated fat 2.88 g, sugar 5.37 g, sodium 205.59 mg, and cholesterol 43.17 mg, a decrease in intakes of fruit by 13.90 g, vegetable 16.76 g, and fiber 0.67 g, a decrease in the Healthy Eating Index-2010 score by 2.32, and an increase in the prevalence of fast-food and full-service restaurant consumption by 10.21% and 17.79%, respectively. Weekend-weekday differences in diet varied by sex, age, race and/or ethnicity, education, income, and body weight status. Conclusions Americans' weekend consumption was associated with increased calorie intake and poorer diet quality.