Abstract BackgroundObservational studies consistently report associations between tobacco use, cannabis use and mental illness. However, the extent to which this association reflects an increased risk of new-onset mental illness is unclear and may be biased by unmeasured confounding. MethodsA systematic review and meta-analysis (CRD42021243903). Electronic databases were searched until November 2022. Longitudinal studies in general population samples assessing tobacco and/or cannabis use and reporting the association (e.g. risk ratio [RR]) with incident anxiety, mood, or psychotic disorders were included. Estimates were combined using random-effects meta-analyses. Bias was explored using a modified Newcastle–Ottawa Scale, confounder matrix, E-values, and Doi plots. ResultsSeventy-five studies were included. Tobacco use...