From 1990 to 1996, a total of 65 patients from whom Corynebacterium diphtheriae had been isolated were reported to the Swiss Federal Office of Public Health. A retrospective review of medical and microbiological records as well as results of ribotyping of available isolates was performed. Twenty-seven patients had acquired their infection without evidence of use of illicit drugs, mostly as a skin infection imported from subtropical areas (20 patients); 38 isolations were associated with intravenous drug use (IVDU) (skin, 15; respiratory tract, 10; blood, 13). Endocarditis was documented in nine patients with bloodstream infection, four of whom died. There were two additional deaths due to overwhelming sepsis. The same ribotype of nontoxigenic C. diphtheriae was found in 31 of the 32 examined isolates associated with IVDU. All non-IVDU isolates had different ribotypes. Among Swiss drug users, a single clone of nontoxigenic C. diphtheriae was found over a period of several years with a high potential to cause severe invasive infection.