Background: It has been hypothesized that monosodium glutamate (MSG), a flavor enhancer, is positively associated with weight gain, which influences energy balance through the disruption of the hypothalamic signaling cascade of leptin action.Objective: The objective was to examine the longitudinal association between MSG consumption and incidence of overweight.Design: Data were collected from the China Health and Nutrition Survey (CHNS), a prospective open-cohort, ongoing nationwide health and nutrition survey, consisting of 10,095 apparently healthy Chinese adults aged 18–65 y at entry from 1991 to 2006. Diet, including MSG and other condiments, was assessed with a weighed food inventory in combination with three 24-h recalls. Incident overweight was defined as a body mass index (BMI; in kg/m2) ≥ 25 or ≥23 based on World Health Organization recommendations for Asian populations. Multilevel mixed-effects models were constructed to estimate change in BMI, and Cox regression models with gamma shared frailty were used to determine the incidence of overweight.Results: The mean follow-up was 5.5 y. The cumulative mean (±SD) MSG intake of 2.2 ± 1.6 g/d was positively associated with BMI after adjustment for potential confounders and cluster effects at different levels (individual, household, and community). The adjusted hazard ratio of overweight was 1.33 (95% CI: 1.01, 1.75; P for trend < 0.01) for participants in the highest quintile of MSG intake compared with those in the lowest quintile after adjustment for age, physical activity, total energy intake, and other major lifestyle factors.Conclusions: MSG consumption was positively, longitudinally associated with overweight development among apparently healthy Chinese adults. Additional studies are needed to elucidate mechanisms of action and to establish causal inference.