The main objective is to study the health-related quality of life (HRQoL) as a positive approach to health in adult adoptees. We will also consider comparison with population norms, relation to chronic medical conditions, the role of sociodemographic variables, and gender differences among the variables in this study.This was a cross-sectional study of 179 adult domestic adoptees from Spain aged between 18 and 44. They were recruited from a longitudinal study, which was on its third wave. They answered an interview and the self-report measure Health Survey Short Form (SF-12). ANOVAs and t test analyses to compare groups, and multiple regression to determine predictors of HRQoL, were performed.Adoptees are not different from the general population in terms of perceived physical health (PH) and mental health (MH). Both PH and MH are related to different variables (e.g., current age is negatively associated with PH, as is the number of chronic medical conditions with MH). Despite the absence of gender differences in MH perception, there were common and different predictor variables for males and females. The number of chronic medical conditions predicts HRQoL regardless of gender. For women, employment is also a predictor, and for men, other variables are being in a romantic relationship, having children, and low income.Adult adoptees are comparable to general population in terms of HRQoL, but there are associated variables (chronic medical conditions and gender) that should be considered. Post-adoption services should promote health and support in life transitions for this group.