The association between drinking 100% fruit juice and long-term weight gain is controversial and has been investigated in few studies. We examined whether 100% fruit juice consumption was associated with weight change in a large prospective cohort of postmenopausal women. We analyzed data from 49,106 postmenopausal women in the United States enrolled in the Women's Health Initiative between 1993 and 1998. Food frequency questionnaires at baseline and year 3 assessed food and beverage intake. Body weight was measured at in-person clinic visits. We used multivariable linear regression to determine the association between change in 100% fruit juice consumption and 3-year weight change over the same time. Covariates of interest included age, demographic factors, smoking, body mass index, hormone replacement therapy, lifestyle factors, change in whole fruit intake, and change in sugar-sweetened beverage intake. The mean weight change was 3.2 lbs. over 3 years. In multivariable adjusted analyses, each 1 serving/day increase in 100% fruit juice intake was associated with a 3-year weight gain of 0.39 lbs. (95% confidence interval: 0.10, 0.69). In conclusion, an increase in 100% fruit juice consumption was associated with a small amount of long-term weight gain in postmenopausal women.