© 2015 Mayo Foundation for Medical Education and Research. Objective To examine the cross-sectional relationships between standing time, obesity, and metabolic syndrome alongside and independent of leisure-time physical activity (LTPA). Participants and Methods The primary study sample consisted of 7075 adult patients (aged 20-79 years) from Cooper Clinic (Dallas, Texas). In this cross-sectional study we assessed the associations between reported standing time and directly measured obesity (body mass index ≥30), elevated waist circumference (men: ≥102 cm; women: ≥88 cm), body fat percentage (men: ≥25%; women ≥30%), and metabolic syndrome (yes/no). In addition, the joint associations of standing and LTPA on each outcome were examined. Multivariable logistic regression adjusting for confounders was used for statistical analyses. Results Standing a quarter of the time or more was significantly associated with reduced odds of an elevated body fat percentage in men (P<.001) and a reduced likelihood of obesity (P<.009) and abdominal obesity (P=.04) in women. In addition, joint association analyses indicated that compared with the reference group (ie, not meeting the physical activity guidelines/standing almost none of the time), men and women who met the physical activity guidelines had lower odds of all obesity outcomes and metabolic syndrome with incremental additions of standing time (ie, a dose-response relationship). Conclusion Standing a quarter of the time per day or more is associated with reduced odds of obesity. The inverse relationship of standing to obesity and metabolic syndrome is more robust when combined with health-promoting LTPA. Prospective studies are warranted to confirm these findings and establish a causal relationship.