Activated protein C (APC) has both anticoagulant and anti-inflammatory properties. In a clinical trial, recombinant APC reduced the mortality rate in patients with severe sepsis by 6.1%. However, the results were felt to be questionable. In sepsis patients with a low risk of death, no beneficial effect of APC was apparent. In addition, concern had been voiced about the increased risk of serious bleeding. A new study was therefore carried out in patients with severe sepsis and a lower risk of death. This trial was terminated prematurely because no benefit from APC could be observed. In a post-hoc analysis, increased mortality was found in patients who had undergone recent surgery. Additional information is required to establish definitively the efficacy and safety of recombinant APC in patients with severe sepsis and a high risk of death.