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Background Tobacco use among United States (US) youth and young adults has declined from historic levels, but cannabis use has not. The importance of cannabis use as a risk factor for tobacco initiation is not known.Methods The association between past 12-month cannabis use in 2017 (study exposure; wave 4) and new-onset regular tobacco use in 2021 (study outcome; wave 6) was examined in a prospective representative US cohort aged 12–24 years who had never regularly used tobacco. Exposed respondents were propensity score matched to unexposed controls on demographics, tobacco use history, perceived harmfulness of cigarettes, mental health symptoms and other measures.Results Among these US youths aged 12–17 years who used cannabis, 32.7% (95% CI: 28.9% to 36.7%) progressed to regular tobacco use in 2021, an increase of 15.6 percentage points (pp) (95% CI: 11.1 pp to 20.2 pp) compared with their matched controls. Among the young adults aged 18–24 years, 14.0% (95% CI: 11.9% to 16.5%) of cannabis users reported regular tobacco use at follow-up, an increase of 5.4 pp (95% CI: 2.6 pp to 8.2 pp) over their matched controls. The matching analysis attributed 13.0% of total new regular tobacco use in the US to cannabis (the population attributable fraction), and estimated that in the absence of cannabis, 509 800 fewer US youth and young adults would have progressed to regular tobacco use in 2021.Conclusion Among US youth and young adults who had never regularly used tobacco, cannabis use in 2017 was associated with a large increase in current regular tobacco use in 2021.