OBJECTIVE: To investigate how adipose tissue alters endogenous hormone levels and may affect events at the ovarian tissue level. METHODS: We assessed current weight, weight at age 18, and adult weight change in relation to ovarian cancer risk among 109,445 participants in the Nurses’ Health Study. Women reported ovarian cancer risk factors and new ovarian cancer diagnoses in biennial mailed questionnaires from 1976 to 1996. Height and weight were queried in 1976, current weight was updated biennially, and weight at age 18 was ascertained in 1980. During 20 years of follow-up and 1,703,474 person-years, 402 cases of epithelial ovarian cancer were confirmed. We used pooled logistic regression to control for age, oral contraceptive use, smoking history, parity, age at menarche, and tubal ligation. RESULTS: We found no evidence of an association between recent body mass index (BMI, kg/m2) and ovarian cancer risk. The multivariable relative risk for women with BMI of 30 kg/m2 or higher versus BMI less than 21 kg/m2 was 1.05 (95% confidence interval 0.73, 1.51). For BMI at age 18, there was no association with ovarian cancer risk overall, but a two-fold increase in premenopausal ovarian cancer risk associated with having a BMI at age 18 of 25 kg/m2 or higher versus BMI less than 20 kg/m2 (relative risk 2.05, 95% confidence interval 1.07, 3.93, P for trend = .01). Adult weight gain was not associated with ovarian cancer risk. CONCLUSION: We found no evidence of an association between recent BMI or adult weight change and ovarian cancer risk. Higher BMI in young adulthood was associated with an increased risk of premenopausal ovarian cancer. If confirmed, these findings suggest an additional reason for avoiding adolescent obesity.