BACKGROUND Diarrhea associated with Clostridium difficile is a health care problem of growing importance in the last few years specially in the hospital environment. The epidemiologic data and factors associated with this disease have not, to date, been sufficiently studied in Spain. METHODS The cases of diarrhea associated with C. difficile reported in 1996 in a tertiary hospital of 1,500 beds were retrospectively reviewed, collecting clinical and epidemiologic data. The technique used for the detection of the C. difficile toxin was EIA Premier. RESULTS One hundred thirty-two patients were included in the study, 83.3% of whom were over the age of 65 years, who had had 148 episodes of diarrhea associated with C. difficile. Most had been admitted into internal medicine (36%) or in the geriatric department (25%) and the remaining in the surgical departments (16.4%) or others (22.6%). The most frequently prescribed antibiotics were third generation cephalosporins (28.6%), clindamycin (17%), quinolones (11.1%) and macrolides (9.1%). Most of the patients received from 2 to 4 antibiotics prior to presenting diarrhea. Thirteen percent of the episodes of diarrhea associated with C. difficile were exclusively treated with withdrawal of the prescribed antibiotic, while the remaining cases were also given specific treatment which in 68.6% of the cases was with metronidazole and 31.4% with vancomycin. No significant difference was observed in the evolution of the patients according to the antibiotic prescribed. CONCLUSIONS Diarrhea associated with C. difficile should be taken into account as a frequent complication of wide spectrum antibiotic treatment, specially in the elderly, immunosuppressed or in patients with pluripathology. With this study the authors wish to underline the need for the judicious use of antibiotics in the hospital environment and aid in the rapid diagnosis of this entity.