To investigate the relation between the fetal environment and endometriosis. P rospective cohort study. Nurses’Health Study II with 10 years of follow-up. Ei ghty-four thousand, four hundred forty-six women aged 25-42 who had never bee n diagnosed with endometriosis, infertility, or cancer at baseline in 1989. Inci dence of laparoscopically confirmed endometriosis according to birthweight, prem aturity, multiple gestation, diethylstilbestrol (DES) exposure, and having been breastfed. During 566,250 woman-years of follow-up, 1,226 cases of laparoscopi callyconfirmed endometriosis were reported among women with no past infertility. After adjusting for age, calendar time, parity, race, and body mass index at ag e 18, we observed a linear increase in the incidence rate with decreasing birthw eight (rate ratio [RR] = 1.3 for birthweight < 5.5 pounds versus 7.08.4 pounds, 95%confidence interval [CI] = 1.01.8, P value, test for trend =. 01). In additi on, women who were born as one of a multiple gestation (i.e., twins or greater n umber) were at increased risk even after controlling for birthweight (RR = 1.7, CI = 1.22.5). The rate of endometriosis was also 80%greater among women exposed to diethylstilbestrol in utero (RR = 1.8, CI = 1.22.8). Neither premature deliv ery nor having been breastfed were associated with the incidence of endometriosi s. None of these effect estimates were modified by infertility status at the tim e of endometriosis diagnosis. The fetal environment is associated with subsequen t laparoscopically confirmed endometriosis in this cohort of US women. To investigate the relation between the fetal environment and endometriosis. P rospective cohort study. Nurses’Health Study II with 10 years of follow-up. Ei ghty-four thousand, four hundred forty-six women aged 25-42 who had never bee n diagnosed with endometriosis, infertility, or cancer at baseline in 1989. Inci dence of laparoscopically confirmed endometriosis according to birthweight, prem aturity, multiple gestation, diethylstilbestrol (DES) exposure, and having been breastfed. During 566,250 woman-years of follow-up, 1,26 cases of laparoscopi callyconfirmed endometriosis were reported among women with no past infertility. After adjusting for age, calendar time, parity, race, and body mass index at ag e 18, we observed a linear increase in the incidence rate with decreasing birthw eight ( Rate of RRR = 1.3 for birthweight <5.5 pounds versus 7.08.4 pounds, 95% confidence interval [CI] = 1.01.8, P value, test for trend = .01). In additi on, women who were born as one of a mul The rate of endometriosis was also 80% greater among women exposed to diethylstilbestrol in utero (RR = 1.7, CI = 1.22.5) = 1.8, CI = 1.22.8). Neither premature deliv ery nor having been breastfed were associated with the incidence of endometriosi s. None of these effect estimates were modified by infertility status at the tim e of endometriosis diagnosis. The fetal environment is associated with subsequential laparoscopically confirmed endometriosis in this cohort of US women.