Prenatal risk, temperamental negative affect, and specific cognitive abilities have all individually been identified as predictors of behavior problems during early childhood, but less is known about their interplay in relation to aggression during toddlerhood. This study examined the main and interaction effects of prenatal risk, negative affect, inhibitory control, attention, and vocabulary in the prediction of aggression in 150 children (75 boys). During pregnancy, a cumulative risk index was calculated based on the presence of 10 well-established maternal risk factors, such as prenatal substance use, maternal psychiatric disorder, and financial problems. Negative affect was measured at 6 and 20 months using maternal report. Child cognition was examined at 30 months using laboratory tasks for inhibitory control and attention, and a questionnaire was administered to assess vocabulary. In addition, mothers reported on their children's aggressive behavior at 30 months. Higher prenatal risk and negative affect at 20 months and, to a lesser extent, at 6 months were related to more aggression at 30 months. Poorer inhibitory control and, to a lesser extent, vocabulary at 30 months also predicted higher levels of aggressive behavior. Two-way interaction effects were found for cumulative risk and inhibitory control, negative affect (at 20 months) and inhibitory control, and negative affect (at 6 months) and vocabulary: aggressive behavior was most pronounced when combinations of high prenatal risk, high negative affect, and poor cognition were present. These results suggest that the impact of prenatal risk and child temperament depends in part on child's cognitive development during toddlerhood.