In a prospective epidemiologic study of a sample of young adults, the authors estimated the risks of being drug-dependent and becoming drug-dependent in relation to the psychosocial work environment encountered during young adulthood. Data were obtained from two young adult assessments of 2,311 children who entered the first grade of primary school in 1985-1986. A total of 1,692 participants completed the first young adult assessment (YAT0) in 2000-2002, and a follow-up young adult assessment (YAT1) was completed approximately 1 year later. Work environments characterized by high job strain (low job control combined with high job demands assessed at YAT0) signaled a 2- to 3-fold excess risk of being drug-dependent (adjusted prevalence ratio = 2.3, 95% confidence interval: 1.4, 4.0). In reestimation for 861 young adults (61% female) with no drug dependence at YAT0, low job control alone was associated with a 2- to 3-fold excess risk of developing drug dependence (adjusted relative risk = 2.6, 95% confidence interval: 1.1, 6.5) between YAT0 and YAT1. The relative risk estimates did not change appreciably with statistical adjustment for demographic covariates, individual drugs used, childhood predispositional traits, job characteristics, and measurements of socioeconomic status at three time points (first grade, adolescence, and young adulthood).