BACKGROUND: Sedentary behaviors are associated with poor health outcomes in the general population, but their clinical impact on adult survivors of childhood acute lymphoblastic leukemia (ALL) has not been characterized to date. In the current study, we described the prevalence of sedentary behaviors in survivors of ALL and examined associations between time spent sedentary and body composition and onset of cardiovascular disease (CVD) risk factors. METHODS: Participants' self-reported screen time (eg, television, computer) and activity as measured by accelerometer were used to determine activity time (sedentary, light activity, and moderate or vigorous physical activity). The percentage of time spent in each activity was compared between 331 survivors of ALL and 330 controls. Associations between time sedentary and body composition were evaluated in survivors using linear regression models. Cox proportional hazard models were used to examine the association between time sedentary at baseline and CVD risk factor onset during follow-up. RESULTS: Survivors spent approximately 65% of their time sedentary, 32% in light activity, and 2% in moderate or vigorous physical activity compared with 67% (P =.04), 30% (P<.01), and 3% (P<.01), respectively, in controls. Among survivors, percentage lean body mass decreased by 1.0% ± 0.4% (P =.01) per 10% increase in time sedentary. Survivors who were sedentary ≥60% per day were found to be at an increased risk of high total cholesterol (hazard ratio, 2.52; 95% confidence interval, 1.12-5.64) and any CVD risk factor (hazard ratio, 1.96; 95% confidence interval, 1.16-3.30). CONCLUSIONS: Sedentary behavior is associated with low lean mass and CVD risk factor development and should be limited in survivors of childhood ALL. Cancer 2018;124:1036-43. © 2017 American Cancer Society.