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Background: Clostridioides difficile infection (CDI) is a disease that is potentially preventable by vaccination. A good knowledge of its epidemiology, which can change over time, is warranted for prevention purposes and to help decision-making on the use of vaccines in public health programs. The objective of the research was to determine the epidemiology of healthcare-associated CDI (HA-CDI) and community-associated CDI (CA-CDI) in hospitalized patients in Spain using point prevalence data. Methods: Point prevalence survey data on infections of hospitalized patients for years 2012-2019 were analyzed. HA-CDI and CA-CDI prevalence rates were calculated. Both HA-CDI and CA-CDI, as well as age group prevalence rates, were examined for trends. Patient comorbidities were tested for association to CDI. Results: The prevalence of CDI in Spanish hospitals has grown exponentially from 14.1% in 2012 to 35.9% in 2019 (cases/10.000 hospitalized patients). Almost two thirds of the cases are of nosocomial onset. This increase was observed for HA-CDI and CA-CDI at an annual rate of 1.11% (CI 95% 1.08-1.15) and 1.09% (CI 95% 1.04-1.13), respectively. Patients 50 years old or older represent 87% of the total number of cases. Patients suffering from neoplasm (OR 1.39), immunodeficiency (OR 3.26), neutropenia (OR 3.70), cirrhosis (OR 1.92) and chronic renal failure (OR 1.91) have a significant increased risk of developing CDI, after adjusting for age. Conclusion: In Spain, the prevalence rate of both HA-CDI and CA-CDI have been increasing. Burden of CDI as well as clinical and epidemiological characteristics of CDI patients will help to support public health decision-making. (C) 2021 Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica. Published by Elsevier Espana, S.L.U. All rights reserved.