Resumen: Background: Multimorbidity is one of the biggest challenges faced by modern medicine, especially when managing older patients who are also often taking multiple medications. Multimorbidity is influenced by social determinants of health, giving rise to health inequalities in the population. Here, we sought to determine the influence of social determinants of health on quality of life in patients with multimorbidity and polypharmacy. Methods and materials: This cross-sectional observational study included 573 patients aged 65–74 with multimorbidity (≥3 diseases) and polypharmacy (≥5 drugs). Corresponding data was taken drawn from the Spanish MULTIPAP study, and included social and demographic variables, and data on health-related quality of life and overall self-perceived health status, assessed using the 5-level version of the EuroQol 5-dimensional questionnaire (EQ-5D-5L). Descriptive, bivariate and multivariate analyses with logistic regression models were performed. Results: Mean patient age was 69.7 years, 55.8% of patients were female, 59.7% belonged to low social classes (V, VI), a monthly income of €1051–€1850 predominated, and the median number of diseases in the same patient was 6. Factors associated with higher quality of life were (odds ratio, OR) male gender (OR = 1.599, p = 0.013), a higher educational level (OR = 1.991, p = 0.036), an absence of urban vulnerability (OR = 1.605, p = 0.017), and the presence of medium social support (OR = 1.689, p = 0.017). Having a higher number of diseases was associated with poorer quality of life (OR = 0.912, p = 0.017). Conclusions: Our findings describe associations between social determinants of health and quality of life in patients aged 65–74 years with multimorbidity and polypharmacy. More illnesses, female gender, a lower education level, urban vulnerability, and less social support are associated with poorer quality of life, underscoring the need for a biopsychosocial approach in patient care. Idioma: Inglés DOI: 10.1371/journal.pone.0297702 Año: 2024 Publicado en: PLoS ONE 19, 9 (2024), e0297702 [15 pp.] ISSN: 1932-6203 Financiación: info:eu-repo/grantAgreement/ES/DGA-FEDER/B01-23R Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI15-00276 Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI15-00572 Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI15-00996 Financiación: info:eu-repo/grantAgreement/ES/ISCIII-RICAPPS/RD21-0016-0015 Financiación: info:eu-repo/grantAgreement/ES/ISCIII-RICAPPS/RD21-0016-0019 Financiación: info:eu-repo/grantAgreement/ES/ISCIII-RICAPPS/RD21-0016-0027 Tipo y forma: Artículo (Versión definitiva) Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)