| Summary: | <i>Clostridioides difficile</i> is a major nosocomial pathogen and has a considerable burden on healthcare systems. Our objective was to determine the transmission patterns of <i>C. difficile</i> in a non-epidemic setting using whole-genome multi-locus sequence typing (wgMLST) and core-genome single-nucleotide polymorphism (cgSNP) analyses. A retrospective study was conducted in a 650-bed university hospital between January 2016 and February 2017. In total, 191 strains isolated from 169 symptomatic <i>C. difficile</i> infection (CDI) patients were analyzed by WGS. Sequences were compared using wgMLST and cgSNP analyses. Genetic data and ward movements were then combined to identify the transmission rate and the type of transmission. The transmission rate varied from 55/169 (19.5%) (wgMLST) to 33/169 (32.5%) (cgSNP). Most transmission was considered cryptic, irrespective of the genetic analysis (38/55 [69.1%] by wgMLST to 25/33 [75.8%] by cgSNP). No transmission within the same ward was observed. In a non-epidemic setting, most <i>C. difficile</i> transmission occurs from sources other than symptomatic CDI patients.
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