Objective: To describe gender differences in self-perceived health and health-related quality of life (HRQoL) in childhood and adolescence in Spain, to compare the results in distinct studies using different HRQoL instruments, and to analyze the influence of sociodemographic factors and reported morbidity on self-perceived health and HRQoL according to gender., Methods: We analyzed data from previous studies of HRQoL: the Child Health and Illness Profile (child and adolescent editions, n=2451), the KIDSCREEN (n=908), and Vecú Perçue et Santé de l'Adolescent (n=1,242). Logistic regression models of worse perceived health (good/fair/poor vs. excellent/very good) and worse HRQoL (less than 0.8 standard deviations from the mean vs. the remaining distribution) were adjusted to analyze gender differences. A summary measure of differences in perceived health according to gender was obtained., Results: The response rates varied among the studies (total sample n=4.601). Girls showed a higher odds ratio (OR) than boys for perceiving worse overall health and physical and emotional health, but a lower OR in school environment dimensions. The overall OR for worse perceived health was 1.28 (95% confidence interval [95%CI]: 0.97-1.68) in younger girls and was 2.17 (95%CI: 1.88-2.51) in adolescent girls., Conclusions: Girls were twice as likely as boys to perceive worse health, as well as worse HRQoL in the physical and emotional dimensions. Gender perspective should be taken into account when implementing preventive and health promotion measures for children and adolescents.