Recently, the incidence and severity of Clostridium difficile infection (CDI) has increased. In cases of fulminant infection, surgery is a viable therapeutic option but associated with high mortality. We sought to examine factors associated with mortality in a large sample of patients with severe CDI that underwent surgery. A retrospective study was conducted in patients with severe CDI undergoing colectomy. Demographics, risk factors, comorbidities, clinical and laboratory data, and time between admission/diagnosis of CDI and colectomy were collected. Conventional markers of severity were evaluated as predictors of mortality. Sixty-four cases were included for analysis. The overall observed mortality rate was 45.3 per cent. Few conventional markers of severity were significantly associated with mortality. Risk factors that correlated with postsurgical mortality were vasopressor use (odds ratio, 3.08; 95% confidence interval, 1.00 to 9.92) and shorter time between diagnosis and surgery (median time, 2 vs 3 days, P = 0.009). This study suggests that a delay in surgery after diagnosis of severe CDI may improve overall outcomes. The finding regarding timing of surgery is contrary to traditional teaching and may be the result of improved medical treatment and stabilization before surgery. Consideration should be given to the importance of timing of colectomy in fulminant CDI, whereas prospective studies should be conducted to elucidate causal relationships.