The Women's Health Initiative (WHI) is a large longitudinal study designed to investigate strategies for the prevention and control of common chronic diseases in postmenopausal women, including cardiovascular disease, cancer, and osteoporotic fractures. The WHI consisted of three overlapping clinical trials of hormone therapy, diet modification to reduce total dietary fat, and calcium/vitamin D supplementation. Women who were ineligible for the hormone therapy or diet modification trials or not interested were invited to participate in the observational study. Women were recruited into WHI from 1993 to 1998 at 40 US clinical centers. WHI enrolled 26,046 underrepresented minority women and 135,762 white women. Women could participate in each trial if eligible. The final enrollment included 27,347 women in the hormone trial; 48,835 women in the diet modification trial; 36,282 women in the calcium/vitamin D trial, and 93,676 in the observational study. After the main study ended in 2005, women were invited to continue follow-up for exposures and outcomes through two extensions to 2020. Proposals were recently submitted to continue follow-up through 2027. Information was collected on an extensive number of risk factors for fractures at baseline and over the follow-up, including fall and fracture history, weight patterns, comorbidities, diet, reproductive history, medications, anthropometry, and biomarkers. Bone mineral density was measured at three WHI clinical centers (n = 11,020) chosen to maximize race/ethnic diversity. WHI encourages outside investigators to make use of the publicly available WHI data and to access the biobank of specimens (www.whi.org).