To determine clinical characteristics and outcome of patients with Clostridium difficile bacteremia (CDB), we identified 12 patients with CDB in 2 medical centers in Taiwan; all had underlying systemic diseases. Five had gastrointestinal diseases or conditions, including pseudomembranous colitis (2 patients); 4 recalled diarrhea, but only 5 had recent exposure to antimicrobial drugs. Ten available isolates were susceptible to metronidazole and vancomycin. Five isolates had C. difficile toxin A or B. Of 5 patients who died, 3 died of CDB. Of 8 patients treated with metronidazole or vancomycin, only 1 died, and all 4 patients treated with other drugs died (12.5% vs. 100%; p = 0.01). C. difficile bacteremia, although uncommon, is thus associated with substaintial illness and death rates.