The objective of the study was to examine the contribution of sociodemographic factors, lifestyle, social network, chronic morbidity and use of healthcare services to the poorer health-related quality of life (HRQL) of women, as compared to that of men, among the older population of Spain. Data were collected by home-based personal interview and physical examination of 3260 subjects representative of the Spanish non-institutionalized population aged 60 years and over. HRQL was assessed with the SF-36 health questionnaire. Relative differences in HRQL between women and men were summarized using odds ratios of suboptimal health (score < 100) on each scale of the SF-36, obtained from logistic regression. The contribution of the variables of interest to the relative differences in HRQL between the sexes was evaluated as the percentage change in the odds ratio before and after adjustment for such variables. The odds ratio of suboptimal health among women versus men was higher than 2 (p < 0.0001) on all SF-36 scales. Adjustment for sociodemographic variables led to a reduction of 23% (95% confidence limits (CL): -38 to -5%) in the odds ratio on the social functioning scale, while adjustment for lifestyle reduced the odds ratio on the general health and social functioning scales by 45% (95%CL: -64 to -15%) and 29% (95%CL: -42 to -13%), respectively. Adjustment for the social network, chronic morbidity and use of healthcare services variables did not lead to significant changes in the odds ratios on any of the SF-36 scales. In general, the contribution of the study variables to differences in HRQL between the sexes was smaller in the oldest age groups. We conclude that sociodemographic and lifestyle factors may explain a substantial part of the differences between women and men in certain HRQL dimensions. Some of these factors, such as the lower educational level and the higher frequency of sedentary lifestyles and obesity among women, are potentially modifiable.