In recent years, it has become feasible to use devices for assessing physical activity and sedentary behavior among large numbers of participants in epidemiologic studies, allowing for more precise assessments of these behaviors and quantification of their associations with health outcomes. Between 2011 and 2015, the Women's Health Study (WHS) used the Actigraph GT3X+ device to measure physical activity and sedentary behavior over 7 days, during waking hours, among 17,708 women (mean age, 72 years) living throughout the United States. Devices were sent to and returned by participants via mail. We describe here the methods used to collect and process the accelerometer data for epidemiologic data analyses. We also provide metrics that describe the quality of the accelerometer data collected, as well as expanded findings regarding previously published associations of physical activity or sedentary behavior with all-cause mortality during an average follow-up of 2.3 years (207 deaths). The WHS is one of the earliest "next generation" epidemiologic studies of physical activity, utilizing wearable devices, in which long-term follow-up of participants for various health outcomes is anticipated. It therefore serves as a useful case study in which to discuss unique challenges and issues faced.