Background: The clinical parameters for the suspicion of Clostridium difficile infections, namely the use of antimicrobials and diarrhea, have a low predictive value for the diagnosis. Aim: To search other clinical variables and determine a clinical prediction model for (Clostridium difficile diarrhea. Patients and methods: All patients to whom a Clostridium difficile study was requested, were prospectively studied during 5 months. Clinical variables of these patients were registered. The diagnosis of Clostridium difficile was done using the cytotoxicity test in fibroblast cultures. Results: Ninety two patients were analyzed and in 26, the diagnosis of Clostridium difficile was confirmed. A logistic regression model disclosed an age over 60 years old, the presence of mucus in the stools and a temperature over 37.8 °C in the previous 24 h, as significant predictors of the infection. The correlation of the model, between the predicted probability and the observed condition, was 81.5%. Conclusions: The presence of the clinical variables identified in this study are associated with a high probability of an infection by Clostridium difficile in patients with diarrhea and the recent use of antimicrobials (Rev Méd Chile 2001; 129: 620-625)