Although selective serotonin reuptake inhibitors (SSRI) are generally effective in reducing impulsive aggression in individuals with intermittent explosive disorder, a large proportion of intermittent explosive disorder patients fail to achieve full remission despite adequate dosage and duration of treatment. Temperament, specifically those associated with negative emotionality (neuroticism, harm avoidance) may predict response to SSRI treatment. The objective of this study was to determine whether baseline neuroticism and harm avoidance scores would be associated with reduced aggression (as measured by the Overt Aggression Scale-Modified [OAS-M] aggression scores) after SSRI treatment. Participants participating in a randomized, placebo-controlled clinical trial of fluoxetine completed the Eysenck Personality Questionnaire (n=57) and the Tridimensional Personality Questionnaire (n=38) before entering the treatment trial. Multiple regression analyses (accounting for baseline OAS-M aggression scores) revealed that pretreatment eysenck personality questionnaire neuroticism and tridimensional personality questionnaire harm avoidance independently and uniquely predicted OAS-M aggression scores at endpoint in the fluoxetine, but not placebo, treated group. These preliminary findings are the first from a placebo-controlled clinical trial to suggest that temperamental factors such as neuroticism and harm avoidance can partly explain the observed variability in treatment response in SSRI treated individuals with impulsive aggression and prompt future prospective studies examining personality dimensions as predictors of outcomes in clinical trials.