Depression, posttraumatic stress, and alcohol use are highly prevalent among firefighters. However, no study has evaluated the interactive effects of depression and posttraumatic stress with regard to alcohol use among firefighters. The current study examined main and interactive effects of depression and posttraumatic stress in terms of alcohol dependence symptoms, positive alcohol dependence ... [Show full abstract] screen, and drinks per occasion. Participants included 2,707 male urban firefighters. There was a main effect of posttraumatic stress in relation to all alcohol-related outcomes and a main effect of depression only for alcohol dependence symptoms. There was a significant interaction of depression and posttraumatic stress with regard to symptoms of alcohol dependence, positive screen for alcohol dependence, and number of drinks per occasion. Interactions were evident above main effects and covariates (age, presence of a spouse/partner, tenure in the fire department, history of active duty in the U.S. armed forces, and racial/ethnic minority status). Overall, heightened depression was positively associated with alcohol-related outcomes for those with lower but not higher levels of posttraumatic stress in all models. Posttraumatic stress and depression may pose unique interactive risks for alcohol dependence in urban male firefighters. Implications for clinical intervention in firefighters are discussed.