A polymorphism in the PER3 (period circadian clock 3) gene has been associated with neuropsychiatric disorders and endophenotypes. We evaluated the possible association of personality domains with the PER3 polymorphism in a sample of healthy subjects: 271 individuals were evaluated with the Big Five Inventory and genotyped for the PER3 Variable Number Tandem Repeat (VNTR) polymorphism. We found a significant association between the PER3 polymorphism and the extraversion personality trait (p = 0.0093). The 5/5 genotype carriers showed higher scores for extraversion. This is the first time that a significant association between the PER3 VNTR polymorphism and extraversion is reported.