(1) Background: Today's society is moving towards active aging, underlining the importance of understanding and improving quality of life (QoL). This QoL in women over the age of 65 years diagnosed with osteoporosis was compared with the QoL of the general population, and risk factors for osteoporosis related to QoL were identified. (2) Methods: This is an observational, descriptive, cross-sectional study with a personal interview. The study population was 704 women over 65 years of age diagnosed with osteoporosis as of 1 November 2018, based on medical records from four health centers of the eastern Valladolid urban health area. This was a random sample of 247 women stratified by health center. Information on osteoporosis risk factors, comorbidities, daily lifestyle habits, and QoL assessed with the EQ-5D was collected. QoL was modeled using sociodemographic variables, lifestyle, and clinical variables. (3) Results: Women with osteoporosis had a positive perception of their health (EQ-5D% VAS 64.9 ± 18.31). High EQ-5D QoL scores were obtained on the dimensions of mobility: 51.6% [95% CI (44.2%, 58.9%)]; self-care: 75.3% [95% CI (68.5%, 81.2%)]; activities of daily living: 71.4% [95% CI (64.4%, 77.6%)]; pain/discomfort: 25.8% [95% CI (19.8%, 32.6%)]; and anxiety/depression: 53.8% [95% CI (46.4%, 61.0%)]. (4) Conclusions: The QoL of the study group was no worse than the QoL of the general population, except for pain/discomfort and anxiety/depression. Age, highest educational level reached, inflammatory diseases, physical activity, and insomnia were independent predictors of QoL in women with osteoporosis.