The D2 dopamine receptor (DRD2) gene has been associated with alcoholism and other drug use disorders. Reduced P300 amplitude has been noted in individuals with psychiatric disorders. Personality variables are also associated with reduced P300 amplitude. The current study was conducted to determine whether variants of the DRD2 would show differential relationships among P300 amplitude and personality traits. The study consisted of 101 adolescent children of alcoholics; 39 carried the A1(+) genotype (A1A1, A1A2) and 62 carried the A1(-) genotype (A2A2). The A1(+) genotype group had higher IQ and Self-Directedness scores than the A1(-) genotype group. As predicted, the negative relationship between Novelty Seeking and Harm Avoidance was present in A1(-) but not A1(+) participants. Additionally, in A1(+) but not in A1(-) participants, there was a negative relationship between Novelty Seeking and Self-Directedness and a positive relationship between P300 amplitude and Cooperativeness. The results suggest that in adolescent children of alcoholics, dopaminergic genetic determinants are critical modifiers of the relationship between neurocognitive and personality endophenotypes proposed as vulnerability markers for substance use disorders.