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Background: The developmental trajectory of problematic substance use (PSU) with associated risk and compensatory factors in adolescence has not been studied intensively.Method: PSU over 7 years between adolescence and adulthood was studied. The data of 593 adolescents (mean age at first measurement occasion: 13.6 years, SD = 1.6; 284 males, 309 females) come from the Zurich Psychology and Psychopathology Study (ZAPPS), covering three measurement occasions over seven years. A probit linear effects model of longitudinal change including various psychosocial predictor variables was used to study the probability of becoming a problematic substance user.Results: The PSU trajectory was nonlinear, rose rapidly through adolescence and flattened out through young adulthood. Age and year of assessment showed the strongest predictive power as risk factors. Among further risk and compensatory predictors, externalizing problem behavior at time one showed a strong increase in PSU.Conclusions: The present study provides new insight into the development of PSU from adolescence to young adulthood including risk and compensatory factors. Age-specific prevention programs should focus on externalizing behavior problems and avoidant coping.