Background: Clostridioides difficile remains the leading cause of infectious diarrhoea in healthcare settings and is an urgent public health threat. In Europe, the epidemiology of C. difficile infection (CDI) has evolved significantly over the past decades.

Aim: This study aimed to provide an updated overview of CDI epidemiology in Belgium between 2013 and 2024.

Methods: Surveillance data were collected from acute hospitals, reporting at least one semester annually and submitting five consecutive samples to the National Reference Centre. Cases occurring 48 h or more after admission were classified as hospital-associated C. difficile infection (HA-CDI). Microbiological analyses included ribotyping, toxin profiling, and antimicrobial susceptibility testing.

Findings: Over the 12-year period, hospital participation remained high, although the number of samples declined. Patient characteristics and recurrence rates remained stable, while the proportion of HA-CDI and complicated cases decreased. CDI incidence increased from 2.24 cases per 10,000 patient-days in 2013 to 2.77 cases in 2024. Strain diversity remained substantial, with over 60 ribotypes (RTs) identified annually. Fifteen RTs accounted for 70% of isolates, with RT014, 020, 002, and 078 alone representing one-third of all strains since 2013, while RT106 and RT154 have emerged more recently. A key finding was the apparent eradication of the hypervirulent RT027 strain. Some less frequent RTs were associated with severe outcomes. All isolates remained susceptible to CDI treatments available in Belgium.

Conclusion: This study highlights major trends in CDI epidemiology including changes in incidence, clinical severity, and RT distribution. Given the epidemiological burden of CDI, continued efforts to monitor CDI evolution are warranted.