Background: Whole genome sequencing (WGS) for C. difficile single nucleotide polymorphism (SNP) typing has been utilised to great effect in research for the last decade. It offers the possibility for ultimate cluster resolution and, with wider routine use, could vastly improve our understanding of the epidemiology of colonisation and disease. A UKAS, ISO:15189, accredited service was introduced in Wales in 2020. Methods: All C. difficile positive (GDH or PCR) samples in Wales should be referred to the Public Health Wales (PHW) UK Anaerobe Reference Unit (UKARU) in Cardiff for culture and typing. Automated extraction of confirmed (MALDI-TOF) C. difficile colonies was undertaken prior to typing. PCR ribotyping was accomplished using capillary gel electrophoresis and WGS using multiple types of Illumina sequencer. WGS data was analysed with a pipeline developed in-house by the PHW Pathogen Genomics Unit using open source software for: quality checking, assembly, reference genome selection and SNP calling. Ribotyping and WGS was performed on all samples until September 2020, after which only WGS was carried out. Results: Of the nearly 44,000 samples tested in Wales during 2020 by PCR or GDH EIA, almost 90% of positive samples were referred to the UKARU (n=2364). Where C. difficile was isolated (n=2113) strains were available for typing from nearly 1500 patients. Ribotyping showed that the top 10 PCR ribotypes in Wales still account for nearly 70% of strains isolated. WGS demonstrated that approximately 30% and 40% of patient strains cluster at the 2- and 5-SNP levels respectively. Genomic clusters involving just two patients were most common, clusters of three and four patients were frequent, and the largest cluster included 13 patients (RT078). Substantial clustering of isolates from within hospitals and the community was seen throughout Wales. Approximately, 10%, 16%, 26% and 48% of clusters were from patients from: the same hospital ward/home address, within hospitals/practices, within health boards (regions), and across health boards respectively. Conclusions: Typing by WGS SNP analysis is expanding our understanding of the potential transmission dynamics of C. difficile in Wales, revealing cryptic clusters of genetically-related samples, and assisting hospital and community acquisition investigation.