Importance Although several longitudinal studies have demonstrated an effect of violent video game play on later aggressive behavior, little is known about the psychological mediators and moderators of the effect. Objective To determine whether cognitive and/or emotional variables mediate the effect of violent video game play on aggression and whether the effect is moderated by age, sex, prior aggressiveness, or parental monitoring. Design, Setting, and Participants Three-year longitudinal panel study. A total of 3034 children and adolescents from 6 primary and 6 secondary schools in Singapore (73% male) were surveyed annually. Children were eligible for inclusion if they attended one of the 12 selected schools, 3 of which were boys’ schools. At the beginning of the study, participants were in third, fourth, seventh, and eighth grades, with a mean (SD) age of 11.2 (2.1) years (range, 8-17 years). Study participation was 99% in year 1. Main Outcomes and Measures The final outcome measure was aggressive behavior, with aggressive cognitions (normative beliefs about aggression, hostile attribution bias, aggressive fantasizing) and empathy as potential mediators. Results Longitudinal latent growth curve modeling demonstrated that the effects of violent video game play are mediated primarily by aggressive cognitions. This effect is not moderated by sex, prior aggressiveness, or parental monitoring and is only slightly moderated by age, as younger children had a larger increase in initial aggressive cognition related to initial violent game play at the beginning of the study than older children. Model fit was excellent for all models. Conclusions and Relevance Given that more than 90% of youths play video games, understanding the psychological mechanisms by which they can influence behaviors is important for parents and pediatricians and for designing interventions to enhance or mitigate the effects.