© 2015 by the American College of Sports Medicine. Purpose The purposes of this study were to examine patterns of objectively measured sedentary behavior in a national cohort of US middle-age and older adults and to determine factors that influence prolonged sedentary behavior. Methods We studied 8096 participants from the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study, a population-based study of black and white adults 45 yr or older. Seven-day accelerometry was conducted. Prolonged sedentary behavior was defined as accumulating 50% or more of total sedentary time in bouts of 30 min or greater. Results The number of sedentary bouts greater than or equal to 20, 30, 60, and 90 min were 8.8 ± 2.3, 5.5 ± 1.9, 1.9 ± 1.1, and 0.8 ± 0.7 bouts per day, respectively. Sedentary bouts greater than or equal to 20, 30, 60, and 90 min accounted for 60.0% ± 13.9%, 48.0% ± 15.5%, 26.0% ± 15.4%, and 14.2% ± 12.9% of total sedentary time, respectively. Several factors were associated with prolonged sedentary behavior in multivariate-adjusted models (odds ratio [95% confidence interval]): older age (65-74 yr: 1.99 [1.55-2.57]; 75 yr or older: 4.68 [3.61-6.07] vs 45-54 yr), male sex (1.41 [1.28-1.56] vs female), residence in nonstroke belt/buckle region of the United States (stroke belt: 0.87 [0.77-0.98]; stroke buckle: 0.86 [0.77-0.95] vs non-belt/buckle), body mass index (BMI) (overweight: 1.33 [1.18-1.51]; obese: 2.15 [1.89-2.44] vs normal weight), winter (1.18 [1.03-1.35] vs summer), and low amounts of moderate-to-vigorous physical activity (MVPA) [0 min·wk-1: 2.00 [1.66-2.40] vs ≥150 min·wk-1). Conclusions In this sample of US middle-age and older adults, a large proportion of total sedentary time was accumulated in prolonged, uninterrupted bouts of sedentary behavior as almost one-half was accumulated in sedentary bouts greater than or equal to 30 min. Several sociodemographic (age, sex, and BMI), behavioral (MVPA), environmental (region), and seasonal factors are associated with patterns of prolonged sedentary behavior.