Background and Purpose: Over the last years an increasing incidence of Clostridium difficile-associated diarrhea (CDAD) has been reported. Especially haematology-oncology patients are at risk of developing CDAD. The aim of this analysis is to determine the incidence of CDAD in radiooncological patients and to find out what relevance CDAD has for the feasibility of the radiooncological treatment, as well as to detect and describe risk factors. Patients and Methods: In a retrospective analysis from 2006 to 2010 34 hospitalized radiooncological patients could be identified having CDAD. The risk factors of these patients were registered, the incidence was calculated and the influence on the feasibility of the radiooncological therapy was evaluated. Induced arrangements for prophylaxis of CDAD were identified and have been correlated with the incidence. Results: The incidence of CDAD in our collective is 1,6%. Most of the patients suffering from a CDAD were treated for carcinoma in the head and neck area. Common risk factors were antibiotics, proton pump inhibitors, cytostatic agents and tube feeding. Beside a high rate of electrolyte imbalance and hypoproteinemia a decrease of general condition was frequent. 12/34 patients had a prolonged hospitalization, in 14/34 patients radiotherapy had to be interrupted due to CDAD. In 21 of 34 patients a concomitant chemotherapy was planned. 4/21 patients could receive all of the planned cycles and only 2/21 patients could receive all of the planned cycles in time. 4/34 patients died due to CDAD. In 4/34 patients an initially curative treatment concept has to be changed to a palliative concept. With intensified arrangements for prophylaxis the incidence of CDAD decreased from 4,0% in 2007 to 0,4% in 2010. Conclusion: The effect of CDAD on the feasibility of the radiotherapy and a concomitant chemotherapy is remarkable. The morbidity of patients is severe with a high lethality. Reducing of risk factors, an intense screening and the use of probiotics as prophylaxis can reduce the incidence of CDAD.