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Background Smoking among adolescents in schools is a major global public health concern. There is limited evidence regarding prevalence and associated factors in Vietnam. Objective To compare the prevalence of smoking and associated factors among in-school adolescents aged 13–17 years in Vietnam between 2013 and 2019. Methods Data were collected from two rounds of the national representative Vietnam Global School-based Student Health Survey (GSHS) conducted in 2013 (n = 3,331) and 2019 (n = 7,690). Logistic regression was used to identify the factors associated with tobacco and electronic cigarette smoking among in-school adolescents. Results There was a significant reduction in the prevalence of current smoking (water pipes and cigarettes) from 5.4% (95% CI: 4.0–7.2) in 2013 to 2.8% (95% CI: 2.2–3.6) in 2019. In 2019, 2.6% of the in-school adolescents reported having used electronic cigarette products 30 days prior to the survey. Factors associated with a significantly higher likelihood of current smoking status included gender, loneliness, suicidal ideation, sexual activity, truancy, and alcohol consumption. Similar patterns were observed for e-cigarettes. Conclusion Smoking among in-school adolescents in Vietnam decreased between 2013 and 2019. Follow-up studies are needed to further investigate causal factors so that future policies and communication programmes can be more effectively targeted to reduce smoking in adolescents.