The authors analyzed the impact of psychosocial work characteristics on the incidence of severe depressive symptoms among 4,133 (49% women) employees from a representative sample of the Danish workforce between 1995 and 2000. Psychosocial work characteristics at baseline included quantitative demands, influence at work, possibilities for development, social support from supervisors and coworkers, and job insecurity. Severe depressive symptoms were measured with the five-item Mental Health Inventory of the 36-item Short-Form Health Survey, with a cutoff point of 52. Women with low influence at work (relative risk (RR) = 2.17, 95% confidence interval (CI): 1.23, 3.82) and low supervisor support (RR = 2.03, 95% CI: 1.20, 3.43) were at increased risk for severe depressive symptoms after exclusion of cases at baseline and adjustment for sociodemographic factors, baseline depression score, and health behaviors. Further adjustments for socioeconomic position did not change the result substantially. Additional analyses showed that a one-standard deviation increase on the influence scale resulted in a 27% decreased risk of severe depressive symptoms. Among men, job insecurity predicted severe depressive symptoms (RR = 2.04, 95% CI: 1.02, 4.07). The findings indicate that the work environment influences the risk of developing severe depressive symptoms and that different factors play a role for men and women.