Purpose: Clostridium difficile colitis (CDC) includes a wide spectrum of presentations and outcomes ranging from mild and self-limited diarrhea, to colitis with abdominal tenderness, to eventually fulminant colitis with potentially fatal outcome. Even though treatment for CDC is theoretically defined and consists of antibiotics for milder forms and surgery for toxic colitis, there is insufficient data regarding appropriate criteria to identify patients who fail conservative treatment and will need a surgical intervention before it is too late. in patients. Our current study aimed at establishing possible predictive indicators favoring surgical over medical treatment for CDC. Methods: Medical records of patients with the diagnosis of CDC were retrospectively reviewed between 01/1999 and 01/2005. Included were patients diagnosed with CDC by ELISA and/or Stool culture. We excluded symptomatic patients with negative C. difficile toxin and patients with incomplete charts. Data collected included general demographics, BMI, APACHE-II score, clinical and laboratory data. End points were (1) the timing and success of conservative treatment, and (2) the eventual need for total or subtotal colectomy, and (3) overall outcome. Statistical analysis was based on the 2-sample Student test and Mann-Whitney Rank-Sum test. For proportions, the p-value is based on the 2-sided Fisher’s Exact test. Results: 86 patients with CDC (M/F 44:42, mean age 53 years, range 68-48) were available for analysis. Pneumonia and UTI were the most frequent cause for the antibiotics that triggered CDC. 76 patients were treated medically only, 10 required surgery. The mortality rate was 3.1% in the conservative and 40% in the operated group, suggesting that the indication for surgery often came too late. The following factors showed statistical significance (P value<0.05) when the surgical vs the non-surgical group were compared: Temperature, heart rate, respiratory rate, WBC, APACHE II score, abdominal tenderness. Treatment with a combination of metronidazole + Vancomycin was more effective than mono-therapy. Factors which did not show a statistically significant impact inclued length of hospital stay, interval after triggering antibiotics, mean blood pressure, and immunossupresion. Conclusion: Based on our data, we identified 7 factors which correlated with the need for an operation in patients with CDC. However, further investigation will need to establish criteria to optimze the timing for intervention.