Although genetics clearly influences the onset of menarche, the association of age at menarche (AAM) with variants in genes related to energy homeostasis remains unexplored. Our aim was to analyze the relationship of the Q223R polymorphism in the leptin receptor gene (LEPR^Q223R) with AAM in a population-based sample of healthy pubertal girls. The study included 338 Spanish girls aged between 11 and 17 yr. Data were collected on AAM. The Q223R polymorphism in LEPR was detected by TaqMan allelic discrimination assays. Girls carrying the RR genotype had a significantly younger AAM (11.5 yr) than those carrying the QR (11.9 yr) or QQ (12.0 yr) genotype (P < 0.05). Furthermore, we found a significantly higher frequency of the RR genotype in girls with an AAM of 11 yr or younger than in girls with an AAM older than 12 yr (23.9% vs. 7.8%, χ² = 11.17, P = 0.0008). Also, the RR genotype frequency in girls with an AAM between 11 and 12 yr was significantly higher than in girls with an AAM older than 12 yr (16.8% vs. 7.8%, χ² = 3.97, P = 0.0046). The Q223R polymorphism in the LEPR gene is associated with variations in AAM among Spanish girls, with the RR genotype being related to earlier onset.