The aim of the present study was to conduct a preliminary study of the Stanford Gender-Related Variables for Health Research (GVHR) adapted to the Spanish population, testing its factor structure, sex factorial invariance and relationship with health variables. Participants were 438 adults between 19–73 years old (M = 31.90, SD = 12.12) who completed the GVHR and measures of health-related quality of life, psychological health, and health-risk behaviors. The confirmatory factorial analysis of the GVHR indicated an acceptable fit to the 7-factor structure as proposed for the North American population. Emotional intelligence and independence factors had low internal consistency, therefore, a five-factor model was tenable in the Spanish population. Sex scalar invariance was tenable, indicating that the factors latent means can be meaningfully compared across sex. Univariate logistic regressions indicated that women reported worse mental and physical health and more health limitations, but this effect dissipated when gender variables were considered. Caregiver and work strain stood out as the variables related to gender that predicted worse health-related quality of life, psychological health, and health-risk behaviors. In conclusion, factorial structure of the GVHR may differ from one culture to another. Additionally, the variables related to gender in the GVHR give a better account of the differences in health compared to biological sex.