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We examined total activity, light activity, and moderate-to-vigorous physical activity (MVPA) as predictors of mortality in a nationally representative sample of older adults. Then we explored the theoretical consequences of replacing sedentary time with the same duration of light activity or MVPA.Using accelerometer-measured activity, the associations between total activity, light activity (100–2019 counts per minute), and MVPA (>2019 counts per minute) counts and mortality were examined in adults age 50 to 79 yr in the National Health and Nutrition Examination Survey, 2003–2006 (n = 3029), with mortality follow-up through December 2011. Cox proportional hazard models were fitted to estimate mortality risks. An isotemporal substitution model was used to examine the theoretical consequences of replacing sedentary time with light activity or MVPA on mortality.After adjusting for potential confounders, including age, sex, race/ethnicity, education, BMI, and the presence of comorbid conditions, those in the highest tertile of total activity counts had one fifth the risk of death of those in the lowest tertile (hazard ratio [HR] = 0.21, 95% confidence interval [CI] = 0.12–0.38), and those in the middle tertile had one third the risk of death (HR = 0.36, 95% CI = 0.30–0.44). In addition, replacing 30 min of sedentary time with light activity was associated with significant reduction in mortality risk (after 5 yr of follow-up: HR = 0.80, 95% CI = 0.75–0.85). Replacing 30 min of sedentary time with MVPA was also associated with reduction in mortality risk (HR = 0.49, 95% CI = 0.25–0.97).Greater total activity is associated with lower all-cause mortality risk. Replacing sedentary time with light activity or MVPA may reduce mortality risk for older adults.