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Purpose To analyze the evolution of the prevalence of polypharmacy and excessive polypharmacy in a Spanish population, and to improve the identification of patients with polypharmacy. Methods: A descriptive, annual cross‐sectional observational study was carried out. Patients: individuals over 14 years of age included in a multiregional primary care database of the Spanish population (BIFAP). Analysis: prescription data. Period 2005‐2015. Variables: proportion of patients with polypharmacy (simultaneous prescription of ≥5 drugs) and excessive polypharmacy (≥10 drugs) for at least 6 months, according to sex and age groups. A trend analysis of the studied period was performed (overall, and by sex and age groups). Results: The data are reported on a comparative basis (2005 vs 2015). Number of patients analyzed: 2664743 vs 4 002 877. The prevalence of polypharmacy increased significantly (2.5% vs 8.9%, P‐value for trend <0.001), being greater in females throughout the study period and in the group aged ≥80 years (P‐value for trends <0.001). The prevalence of excessive polypharmacy also increased significantly (0.1% vs 1%, P‐value for trend <0.001), being higher in the group aged ≥80 years (P‐value for trend <0.001). The proportion of patients with no chronic treatment decreased (80.2% vs 63.1%). Conclusions: The prevalence of polypharmacy in this Spanish population has tripled in the period 2005‐2015, while excessive polypharmacy has increased 10‐fold. These increments are seen in both sexes and in all age groups, particularly in individuals over 80 years of age. The proportion of patients without chronic treatments has decreased. [ABSTRACT FROM AUTHOR]