Invasive disease due to Corynebacterium diphtheriae is rare in North America. Here we describe the emergence of a predominant clone of a nontoxigenic strain of C. diphtheriae in the impoverished population of Vancouver's downtown core. This clone has caused significant morbidity and contributed to at least two deaths. Over a 5-year period, seven cases of bacteremia due to C. diphtheriae were detected in patients admitted to Vancouver hospitals. Injection drug use, diabetes mellitus, skin colonization/infection with C. diphtheriae, and homelessness all appeared to be related to the development of bacteremia with the organism. Ribotyping of isolates recovered from blood culture revealed a predominant ribotype pattern that has not previously been reported in North America.