A Cochrane review included 6 studies with a total of 6781 participants (6307 adults and 474 paediatric patients). For 28-day mortality, activated protein C (APC) did not reduce the risk of death in adult participants with severe sepsis (pooled RR1.00, 95% CI 0.88 to 1.14). APC did not significantly affect in-hospital mortality (RR 1.01, 95% CI 0.87 to 1.16; I2 = 20%). APC use was associated with a higher risk of bleeding (RR 1.47, 95% CI 1.09 to 2.00). APC did not significantly affect serious adverse events (RR 1.04, 95% CI 0.92 to 1.18; I2 = 0%).