Firefighters constitute an understudied occupational group that are exposed to a great deal of occupational stress including potentially traumatic stress. As such, higher prevalence rates of posttraumatic stress disorder (PTSD) and substance use disorders have been observed within this population; however, very little is known about the trajectories of health-risk behaviors among firefighters in response to occupational stress over time. The present study enrolled 322 fire service recruits from 7 urban U.S. professional fire departments and followed them through the first 3 years of service. All enrollees were free of Axis I psychopathology at the time of baseline assessments, which were conducted while participants were still enrolled in the fire academy. We hypothesized that: (a) firefighters who used tobacco would have higher levels of alcohol use over time; and (b) firefighters with higher levels of traumatic exposure and mental health symptoms would evidence a stronger multisubstance risk pattern. Analyses provided support for our first hypothesis and revealed that depressive symptoms (but neither trauma exposure nor PTSD symptoms) moderated the alcohol-tobacco relationship. The clinical and public safety implications of these results are discussed. (PsycINFO Database Record