The majority of leisure time is spent in sedentary behaviors such as television viewing. Studies have documented that prolonged leisure-time sitting is associated with higher risk of mortality-total, cardiovascular disease, cancer, and "all other causes"-but few have examined the "other" causes of death in detail. To examine associations of leisure-time sitting with risk of specific causes of death, we analyzed data from the Cancer Prevention Study II (CPS-II) Nutrition Cohort, a prospective US cohort including 127,554 men and women who were free of major chronic disease at study entry, and among whom 48,784 died during 21 years of follow-up (1993-2014; median follow-up, 20.3 years, interquartile range, 4.6 years). After multivariable adjustment, prolonged leisure-time sitting (≥6 vs. <3 hours per day) was associated with higher risk of mortality from all causes, cardiovascular disease (including coronary heart disease and stroke-specific mortality), cancer, diabetes, kidney disease, suicide, chronic obstructive pulmonary disease, pneumonitis due to solids and liquids, liver, peptic ulcer and other digestive disease, Parkinson disease, Alzheimer disease, nervous disorders, and musculoskeletal disorders. These findings provide additional evidence for associations between a broad range of mortality outcomes and prolonged sitting time. Given the pervasive nature of sitting in the contemporary lifestyle, this study further supports the recommendation that encouraging individuals to reduce sedentary time may provide health benefits.