Findings from preclinical and clinical research support the involvement of central noradrenergic dysregulation in the etiology of attention deficit hyperactivity disorder (ADHD). Previous studies have suggested that the alpha-2C-adrenergic receptor gene (ADRA2C) is associated with ADHD. The aims of this study were to examine the association between the ADRA2C (GT)n repeat polymorphism (STR marker adra2c1) and ADHD in a Korean sample. In this case-control and family-based association study, we assessed 184 ADHD probands, 150 normal controls, and 98 trios. There were no significant differences in the allele frequencies of the ADRA2C polymorphism between the ADHD and control groups (p > 0.05). The overall allele-wise transmission disequilibrium test (TDT) analysis showed statistical significance (chi2 = 19.07, p = 0.025). We found a trend for preferential transmission of the 183-bp allele (chi2 = 3.72, p = 0.054), and a significantly lower-than-expected rate of transmission of the 187-bp allele (chi2 = 6.26, p = 0.012). With regard to the temperament profiles of the Junior Temperament and Character Inventory (JTCI), the ADHD subjects with the 183/183 genotype at the ADRA2C polymorphism showed a trend toward a lower score in the Novelty Seeking (p = 0.020) profile than did those with the other genotypes. Our findings provide important evidence that the ADRA2C polymorphism is involved in the etiology of ADHD in Korean subjects. In addition, our results provide evidence that the temperament of Novelty Seeking and ADHD might share molecular genetic characteristics related to the noradrenergic system.