Background: Difficulties with affect regulation and impulse control have a strong influence on violence. The objective of this study was to determine whether baseline depression and impulsivity predict aggression and whether they predict differential response to antiaggressive treatment. This is important, as we lack knowledge as to the selection of antipsychotics for the treatment of aggression. Methods: Physically aggressive inpatients with schizophrenia who received an evaluation of depression and impulsivity at baseline were randomly assigned in a double-blind, parallel group, 12-week trial to clozapine, olanzapine, or haloperidol. Trait impulsivity was measured by the Barratt Impulsiveness Scale; depression by the Positive and Negative Syndrome Scale Depression factor. The number and severity of aggressive events, as measured by the Modified Overt Aggression Scale (MOAS), were the outcome measures. Results: Baseline depression and impulsivity predicted higher levels of aggression, as measured by the MOAS total score, over the 12-week treatment period across all 3 medication groups. In addition, there was a strong interaction effect between baseline depression/impulsivity and medication grouping in predicting MOAS score. In particular, when higher depression and impulsivity were present at baseline, patients on haloperidol presented with more aggression than patients on the other 3 medications. Conclusions: Depression and impulsivity are important predictors of aggression and of differential response to antiaggressive treatment. This is most likely due to the medications’ dissimilar neurotransmitter profiles. By identifying patients who will respond better to a given medication, we will be able to develop individualized strategies for the treatment of violent behavior.