Background: The cumulative effect of too much sedentary behavior may contribute to weight gain and obesity. Objective: The aim of this study was to conduct a systematic review and meta-analysis of prospective cohorts and randomized controlled studies to determine the association between sedentary behavior and body weight and obesity in adults. Data sources and study selection: Relevant studies were identified from searches of the MEDLINE, Embase, AMED and PubMed databases up to May 2017, and by manual searches of in-text citations. Studies that evaluated the association in adults between sedentary behavior and body weight or obesity, while controlling for physical activity, were included. Overall, 31 publications met the eligibility criteria, including 23 prospective cohort studies with data that could be extracted for a quantitative meta-analysis, and a single randomized controlled trial. Results: There were no significant associations between sedentary behavior and any measure of body weight or obesity, with the exception of waist circumference. For the latter outcome, over a 5-year follow-up period, each 1 h per day increase-from baseline to follow-up-in sedentary behavior was associated with a 0.02 mm [95% confidence interval (CI) 0.01-0.04; p = 0.001) increase in waist circumference. The odds ratio of becoming overweight or obese was 1.33 (95% CI 1.11-1.60; p = 0.001) in the highest compared with lowest categories of sedentary behavior. Conclusions: Meta-analysis of data from prospective cohort studies showed small, inconsistent and non-significant associations between sedentary behavior and body weight.