Over the last decade, there has been a dramatic increase in the incidence and severity of Clostridium difficile infection (CDI) in North America and Europe associated with the emergence of a fluoroquinolone-resistant epidemic C. difficile strain known as PCR ribotype (RT) 027. In Australia, RT 027 is rare but the incidence of both hospital and community-associated CDI is on the rise, with younger individuals with no traditional risk factors acquiring the infection. We present three cases of CDI caused by an unusual RT of C. difficile, RT 251. All cases presented with severe diarrhea in the community. While one patient was elderly and suffered multiple comorbidities, two were young and previously healthy. One of the young cases underwent a colectomy, suffered multiple organ failure and died. Isolates were confirmed by PCR and ribotyping as RT 251 strains that encode the toxin genes tcdA (toxin A), tcdB (toxin B), cdtA and cdtB (binary toxin). Culture supernatants caused cytopathic effect on Vero cells in vitro, but notably toxin production was less than that seen with both virulent RT 027 and strain CD 630 ─ a known low-level toxin producer. Phenotypic resistance to clindamycin and erythromycin was observed in a single isolate (MICs 8mg/L and ≥ 256mg/L, respectively). Whole genome sequencing revealed the strains were clonal with 0-5 single nucleotide variants between isolates, and that RT 251 was closely related to the epidemic strain RT 027. In a murine model, infection with RT 251 resulted in severe disease symptoms that resembled those observed with RT 027. Mice suffered rapid onset of disease, marked weight loss by 36 h and death within 48 h post-infection. These data suggest a common reservoir of infection and the need to carefully monitor this ribotype.