Background: Evidence that higher sedentary time is associated with higher risk for cardiovascular disease (CVD) is based mainly on self-reported measures. Few studies have examined whether patterns of sedentary time are associated with higher risk for CVD. Methods: Women from the OPACH Study (Objective Physical Activity and Cardiovascular Health; n=5638, aged 63–97 years, mean age 79±7 years) with no history of myocardial infarction or stroke wore accelerometers for 4 to 7 days and were followed up for up to 4.9 years for CVD events. Average daily sedentary time and mean sedentary bout duration were the exposures of interest. Cox regression models were used to estimate hazard ratios (HRs) and 95% CIs for CVD using models adjusted for covariates and subsequently adjusted for potential mediators (body mass index, diabetes mellitus, hypertension, and CVD risk biomarkers [fasting glucose, high-density lipoprotein, triglycerides, and systolic blood pressure]). Restricted cubic spline regression characterized dose-response relationships. Results: There were 545 CVD events during 19 350 person-years. With adjustment for covariates, women in the highest (≈11 h/d or more) versus the lowest (≈9 h/d or less) quartile of sedentary time had higher risk for CVD (HR, 1.62; 95% CI, 1.21–2.17; P trend <0.001). Further adjustment for potential mediators attenuated but did not eliminate significance of these associations ( P trend <0.05, each). Longer versus shorter mean sedentary bout duration was associated with higher risks for CVD (HR, 1.54; 95% CI, 1.27–2.02; P trend=0.003) after adjustment for covariates. Additional adjustment for CVD risk biomarkers attenuated associations, resulting in a quartile 4 versus quartile 1 HR of 1.36 (95% CI, 1.01–1.83; P trend=0.10). Dose-response associations of sedentary time and bout duration with CVD were linear ( P nonlinear >0.05, each). Women jointly classified as having both high sedentary time and long bout durations had significantly higher risk for CVD (HR, 1.34; 95% CI, 1.08–1.65) than women with low sedentary time and short bout duration. All analyses were repeated for incident coronary heart disease (myocardial infarction or CVD death), and associations were similar, with notably stronger HRs. Conclusions: Both high sedentary time and long mean bout durations were associated in a dose-response manner with increased CVD risk in older women, which suggests that efforts to reduce CVD burden might benefit from addressing either or both components of sedentary behavior.