A variable (GT)n repeat in the 5′-regulatory region of N-methyl-D-aspartate GRIN2A subtype has recently been identified and associated with psychiatric disorders. In this study, we examined the association of this polymorphism with alcohol dependence. Subject–control analysis included 206 alcohol-dependent and 168 control subjects. Average observed repeat numbers and genotype distributions were significantly different (P-value = 0.001) in alcohol-dependent subjects versus control subjects. Short alleles were significantly less frequent among alcohol-dependent subjects (odds ratio = 0.58, P-value = 7 × 10−4). These results could be replicated in an independent sample of 116 alcohol-dependent subjects. For the first time, a significant association was identified between this polymorphism and alcoholism.