The aim of this study was to test efficacy and safety of intravenous (IV) valproate for aggression in children and adolescents with mood or conduct disorder and concomitant substance abuse. Six patients received a 20 mg/kg dose of IV valproic acid as an add-on therapy to their standard therapy with second-generation antipsychotics and benzodiazepines. Agitation and general psychopathology were measured at baseline and after the first injection using the Modified Overt Aggression Scale, the Brief Psychiatric Rating Scale, and the Children's Global Assessment Scale. The findings suggested that in emergency psychiatry clinical settings, IV valproate was effective in reducing agitation and aggressive behaviors with a good tolerability profile and better treatment compliance.