In the last decade a large number of studies focused on the recognition of gene variants modulating temperamental traits. The gene coding for the estrogen receptor alpha (ESR1) appears to be an interesting candidate and it has been found to be linked to Harm avoidance (HA). The aim of the present study was to investigate whether the ESR1 TA dinucleotide repeat polymorphism is associated with HA temperamental trait in a sample of Caucasian University students. One hundred ninety healthy subjects were genotyped for ESR1 TA dinucleotide repeat polymorphism and were administered the Temperament and Character Inventory (TCI). ESR1 TA repeat lengths were dichotomized into short and long categories. ANOVA was used to examine the influence of ESR1 variants (short/long) on the means of the TCI HA scores. HA was significantly associated with age and gender in our sample, being higher in older and female subjects. In the global sample as well as in men and women separately, individuals carrying the S/S variant showed significantly higher HA scores. Further analysis on the HA subscales revealed that specific differences could exist between men and women. Our results further suggest a possible role of ESR1 variants on HA. Further research is needed to replicate our findings as well as to better explore the neuro-biological mechanisms of the modulation of ESR1 on HA.