Background: Physical activity decreases and time spent sedentary increases with age. Evidence suggests that even modest levels of physical activity may reduce the risk of disease, disability, and death in older adults. We aimed to quantify the risk of low physical activity and high sedentary behavior on disease (defined as having cardiovascular disease, stroke, cancer, diabetes, and/or hip fracture), mobility disability, and death in women ≥85 years of age. Methods: Women from the Women’s Health Initiative Clinical Trials (CTs) and Observational Study (OS) programs born before September 1, 1925 (therefore, ≥85 years old by September 1, 2010) were categorized into mutually-exclusive groups: 1) no disease and no disability (“healthy”); 2) ≥1 disease but no disability (“diseased”); 3) mobility disabled with or without disease (“disabled”); and 4) died before age 85 years. The associations of baseline physical activity levels, in metabolic equivalent hours/week (MET-hrs/wk), for CT and OS women (n=27,998) and baseline hours/day spent sitting for OS women (n=16,889) comparing “healthy” (reference group) to the other three outcomes were evaluated using polytomous logistic regression. Odds ratios (OR) and 95% confidence intervals (CI), adjusted for race/ethnicity, education, marital status, and baseline age, hormone therapy use, smoking status, alcohol use, body mass index, and depression, were estimated. Results: Baseline age range was 68-81 years. Mean (SD) baseline physical activity level was 12 (13) MET-hrs/wk (range: 0-134). Mean (SD) baseline MET-hrs/wk for women classified as healthy, diseased, disabled, and died were 15 (14), 13 (13), 10 (12), and 11 (12), respectively (p-trend<0.001). Compared to women in the highest physical activity quartile (≥17.5 MET-hrs/wk), the risk of being diseased, disabled, or of dying relative to being healthy increased in a dose-dependent manner for women in the lower three physical activity quartiles. Women in the lowest quartile (0-<2.5 MET-hrs/wk) had the highest risk, with adjusted ORs (95% CIs) for being diseased, disabled, and of dying of 1.4 (1.3-1.6), 2.4 (2.1-2.7), and 2.2 (1.9-2.5), respectively. Similarly, women who spent ≥8 hours/day sitting had a higher adjusted odds (95% CI) of being disabled (1.3 (1.1-1.4)) and of dying (1.2, (1.0-1.3)), but were not at increased risk of being diseased (1.0 (0.9-1.1)), compared to women who spent ≤5 hours/day sitting. Conclusions: For older women, engaging in modest levels of physical activity and avoiding long periods of sedentary behavior may improve the chance of surviving to age 85 years without disease and mobility disability. Since physical activity and sedentary lifestyle are modifiable behaviors, these findings help inform public health strategies aimed at preventing disease and disability in older women, which may help to reduce healthcare costs and improve overall quality of life.