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Diagnosis of mental illness (MI) inconsistently predicts aggressive behavior although co-occurrence of substance use appears to increase the frequency of aggression in MI populations. We propose that alcohol use should moderate the relationship between mental disorders marked by deficits in self-control and aggression and victimization. In the present study, alcohol use, physical aggression perpetration, physical aggression victimization, injury and psychiatric symptoms were assessed in a sample of 297 substance use disorder patients (102 women; Mage = 38.9, SD = 20.2) recruited from a residential treatment facility. Negative binomial regression analyses examined the relationship of physical aggression, victimization, and injury over the previous 12 months to symptoms of bipolar mania, psychosis, posttraumatic stress disorder, antisocial personality disorder (ASPD), and daily volume of alcohol consumed. Consistent with past research relating MI to aggression, rates of victimization were higher than rates of perpetration. Results demonstrated that alcohol use moderated the relationship of manic symptoms of bipolar disorder to perpetration of aggression and causing injury to others. Three way-interactions between gender, alcohol use, and both psychotic and ASPD symptoms were related to victimization. The combination of heavy alcohol use and increased psychotic or ASPD symptoms was related to greater victimization for women but not for men. Women with more psychotic symptoms who were heavy drinkers were also more likely to report causing injury to another person. Results were generally consistent with the multiple-thresholds model of alcohol-related aggression; however, the moderating effects of alcohol use were dependent on gender and type MI.