Background:Data are sparse regarding the impacts of habitual physical activity (PA) and sedentary behavior on cardiovascular (CV) risk in older adults with mobility limitations. Methods and Results:This study examined the baseline, cross-sectional association between CV risk and objectively measured PA among participants in the Lifestyle Interventions and Independence for Elders (LIFE) study. The relationship between accelerometry measures and predicted 10-year Hard Coronary Heart Disease (HCHD) risk was modeled by using linear regression, stratified according to CVD history. Participants (n=1170, 79±5 years) spent 642±111 min/day in sedentary behavior (ie, <100 accelerometry counts/min). They also spent 138±43 min/day engaging in PA registering 100 to 499 accelerometry counts/min and 54±37 min/day engaging in PA ≥500 counts/min. Each minute per day spent being sedentary was associated with increased HCHD risk among both those with (0.04%, 95% CI 0.02% to 0.05%) and those without (0.03%, 95% CI 0.02% to 0.03%) CVD. The time spent engaging in activities 100 to 499 as well as ≥500 counts/min was associated with decreased risk among both those with and without CVD (P<0.05). The mean number of counts per minute of daily PA was not significantly associated with HCHD risk in any model (P>0.05). However, a significant interaction was observed between sex and count frequency (P=0.036) for those without CVD, as counts per minute was related to HCHD risk in women (b=-0.94, -1.48 to -0.41; P<0.001) but not in men (b=-0.14, -0.59 to 0.88; P=0.704). Conclusions:Daily time spent being sedentary is positively associated with predicted 10-year HCHD risk among mobility-limited older adults. Duration, but not intensity (ie, mean counts/min), of daily PA is inversely associated with HCHD risk score in this population-although the association for intensity may be sex specific among persons without CVD.