The influence of unemployment and adverse work conditions on the course of psychopathology after a mass disaster is unclear. We recruited a representative sample of adults living in the New York City metropolitan area six months after the September 11 attacks and completed follow-up interviews on 71% of the baseline sample six months later (N = 1939). At follow-up, posttraumatic stress disorder (PTSD) persisted in 42.7% of the 149 cases with PTSD at baseline. In multivariable models, unemployment at any time since baseline predicted PTSD persistence in the entire cohort (P = 0.02) and among persons employed at follow-up (P = 0.02). High levels of perceived work stress predicted PTSD persistence among persons employed at follow-up (P = 0.02). Persons unemployed in the aftermath of a disaster may be at risk for poor mental health in the long-term.