Little is known about the long-term effects of dietary energy density (ED) on weight gain.The objective was to assess the long-term relation between changes in dietary ED and age-related weight gain.We conducted a prospective study of 50 026 women (x +/- SD age: 36.5 +/- 4.6 y) in the Nurses' Health Study II followed from 1991 to 1999. Dietary ED and body weight were ascertained in 1991, 1995, and 1999. Total dietary ED was calculated by dividing each subject's daily energy intake (kcal) by the reported weight (g) of all foods consumed.Dietary ED was positively correlated with saturated fat (r = 0.16), trans fat (r = 0.15), and the glycemic index (r = 0.16), but was inversely correlated with vegetable protein (r = -0.30), vegetables (r = -0.27), and fruit (r = -0.17). ED was not significantly correlated with total fat intake as a percentage of energy (r = 0.08). Women who increased their dietary ED during follow-up the most (5th quintile) had a significantly greater multivariate-adjusted weight gain than did those who decreased their dietary ED (1st quintile) (8-y time period: 6.42 kg compared with 4.57 kg; P for trend < 0.001). However, the amount of weight change over time varied considerably according to the ED values of individual foods and beverages.A high dietary ED reflects a dietary pattern higher in saturated and trans fats and refined carbohydrates. Increases in dietary ED were associated with greater weight gain among middle-aged women during 8 y of follow-up. However, public health recommendations cannot be made simply on the basis of ED values of individual foods and beverages.