Background: The transition from late adolescence to early adulthood (16-20 years) represents a time of exploration and self-discovery for many young people. As such, it is often associated with experimentation in substance use. Vocational students in particular report high substance use. Thus, the aim of this study is to examine patterns and trajectories of their substance use behavior. Methods: On two occasions (interval 18 months), we investigated 5214 students (M = 19.39 years; 54% male) from 49 vocational schools in seven German federal states. We identified classes of substance use and trajectories via latent transition analysis, controlling for gender, age, and socio-economic status. Additionally, we investigated work-related (job demands/stress/satisfaction) and psychopathological (depressive symptoms) predictors of substance use via multinomial regressions. Results: We found three latent stages of substance use: low use (baseline: 43%/follow-up: 44%), mainly alcohol use (50%/45%), and polysubstance use (7%/11%). Over time, 10% of alcohol users at baseline transitioned to polysubstance use at follow-up, while there were smaller transition rates (2-9%) between the other stages. Compared to low use, polysubstance use at follow-up was predicted by high job stress (aOR = 1.45, 1.07-1.96) at baseline. Conclusions: High alcohol use is associated with bidirectional transitions in young adults. Hence, future research needs to identify mechanisms of change to identify protective factors. Regarding vocational practice, early stress management seems to be a viable path to prevent polysubstance use in vocational students. (C) 2016 Elsevier Ltd. All rights reserved.