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Background Few studies have evaluated the association between early life adiposity and ovarian cancer risk. Adiposity during different periods of life may be differentially associated with the risk. Patients and methods We prospectively followed 133 526 women in the Nurses' Health Study (NHS; 1980–2012) and NHSII (1989–2013). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident ovarian cancer (N  = 788) according to validated measures for early life adiposity [body mass index (BMI) at age 10 imputed from somatotype and recalled BMI at age 18) as well as BMI change between age 10 and 18 and after age 18 (current weight assessed on every biennial questionnaire since baseline). Results After mutual adjustment for BMI at age 10, BMI at age 18 and current BMI, the HR (95% CI) for ovarian cancer risk per 5 kg/m2 was 0.84 (0.74–0.96) for BMI at age 10 (P -trend = 0.01), 1.17 (1.03–1.33) for BMI at age 18 (P -trend = 0.02), and 1.06 (0.99–1.14) for current BMI (P -trend = 0.08). However, the inverse association with BMI at age 10 was attenuated after adjusting for BMI change between age 10 and 18 and BMI change after age 18 (HR per 5 kg/m2: 1.04; 95% CI 0.91–1.20; P -trend = 0.55). By contrast, BMI change between age 10 and 18 was strongly positively associated with ovarian cancer risk (HR per 5 kg/m2 increase: 1.24; 95% CI 1.11–1.39; P -trend = 0.0002), whereas BMI change since age 18 was only slightly associated with risk (HR per 5 kg/m2 increase: 1.06; 95% CI 0.99–1.14; P -trend = 0.10). These associations were in general stronger for premenopausal cases or non-serous tumors. Conclusion Early life changes in adiposity were more strongly associated with ovarian cancer risk than adulthood changes. The specific mechanisms underlying the associations with adiposity changes during early life warrant further investigation. [ABSTRACT FROM AUTHOR]