Purpose: This study aimed to describe the 5-yr longitudinal change in moderate-to-vigorous physical activity (MVPA) among urban adolescents in Ho Chi Minh City, Vietnam, and to identify individual, family, and environmental factors associated with changes in MVPA. Methods: The Ho Chi Minh City Youth Cohort is a 5-yr longitudinal cohort with systematic random sampling of 759 students (48% boys) from 18 junior high schools in Ho Chi Minh City, conducted from 2004 to 2009. All measures were taken on five separate occassions. MVPA was assessed by self-report and accelerometry. Data were analyzed using multilevel linear regression models with estimation by generalized linear latent and mixed models. Results: Overall, after adjusting for covariates, students' accelerometer-based MVPA reduced 38% per annum (rate ratio = 0.62, 95% confidence interval (CI) = 0.59-0.64). Boys spent 2.9 times more in MVPA (rate ratio = 2.94, 95% CI = 2.63-3.22) than their female peers. Compared with normal-weight adolescents, overweight and obese adolescents were doing 40% (rate ratio = 0.60, 95% CI = 0.53, 0.67) less MVPA. Conclusions: MVPA significantly declined among Vietnamese adolescents with age. This finding is similar to those reported among Western adolescents and suggests that strategies to promote physical activity in adolescents are a priority in Vietnam because economic transitioning potentially increases the risk of adopting unhealthy lifestyle behaviors associated with obesity and chronic diseases.