Associations between individual foods or nutrients and oxidative markers have been reported. Comprehensive measures of food intake may be uniquely informative, given the complexity of oxidative systems and the possibility of antioxidant synergies. We quantified associations over a 20-year history between three food-based dietary patterns (summary measures of whole diet) and a plasma biomarker of lipid peroxidation, F2-isoprostanes, in a cohort of Americans ages 18–30 at year 0 (1985–1986). We assessed diet at years 0, 7, and 20 through a detailed history of past-month food consumption and supplement use and measured plasma F2-isoprostanes at years 15 and 20. We created three dietary patterns: (1) a priori (“a priori diet quality score”) based on hypothesized healthfulness of foods, (2) an empirical pattern reflecting high fruit and vegetable intake (“fruit–veg”), and (3) an empirical pattern reflecting high meat intake (“meat”). We used linear regression to estimate associations between each dietary pattern and plasma F2-isoprostanes cross-sectionally (at year 20, n=2736) and prospectively (year 0/7 average diet and year 15/20 average F2-isoprostanes, n=2718), adjusting for age, sex, race, total energy intake, education, smoking, body mass index, waist circumference, physical activity, and supplement use. In multivariable-adjusted cross-sectional analysis, the a priori diet quality score and the fruit–veg diet pattern were negatively, and the meat pattern was positively, associated with F2-isoprostanes (all p values <0.001). These associations remained statistically significant in prospective analysis. Our findings suggest that long-term adherence to a diet rich in fruits and vegetables and low in red meat may decrease lipid peroxidation.