The NCI DES Follow-up Study is a nationwide research study following three generations of individuals to investigate the long-term health effects of diethylstilbestrol (DES) exposure in the United States. As the largest ongoing study on long-term health and DES exposure, it follows over 21,000 DES-exposed and unexposed participants who in 1992-1994 were drawn from prenatal records or one of five previously studied cohorts: the DESAD Cohort, the Women’s Health Study Cohort, the Mayo Clinic Cohort, the Dieckmann Cohort, or the Horne Cohort. The first generation (mothers) comprises women exposed during pregnancy: 3,763 second generation women, including 2,517 exposed to DES in utero, and 1,246 unexposed. The second generation (daughters and sons) comprises 4,029 sons (2,640 exposed, 1,389 unexposed) and 3,808 daughters (2,449 exposed, 1,359 unexposed). The third generation (granddaughters) comprises 793 daughters of prenatally exposed women, including 463 exposed and 330 unexposed. All cohorts are continuously followed up as a combined cohort. The DES mothers cohort received one combined cohort questionnaire in 1994 and has been followed passively for deaths since that time. The DES sons and daughters cohort have been followed by periodic mailed questionnaire in 1994, 1997, 2001, 2006, 2011, and 2016 for assessment of changes in health status and changes in exposures. The DES granddaughters' cohort baseline took place in three phases as females reached 18 years of age in 2001, 2009, or 2019.