Severe sepsis is one of the most common causes of acute lung injury (ALI) and is associated with high mortality. The aim of the study was to see whether a protective strategy based approach with a plateau pressure <30 cmH(2)O was associated with lower mortality in septic patients with ALI in the Surviving Sepsis Campaign international database. A retrospective analysis of an international multicentric database of 15,022 septic patients from 165 intensive care units was used. Septic patients with ALI and mechanical ventilation (n=1,738) had more accompanying organ dysfunction and a higher mortality rate (48.3% versus 33.0%, p<0.001) than septic patients without ALI (n=13,284). In patients with ALI and mechanical ventilation, the use of inspiratory plateau pressures maintained at <30 cmH(2)O was associated with lower mortality by Chi-squared test (46.4% versus 55.1%, p<0.001) and by Kaplan-Meier and log-rank test (p<0.001). In a multivariable random-effects Cox regression, plateau pressure <30 cmH(2)O was significantly associated with lower mortality (hazard ratio 0.84, 95% CI 0.72-0.99; p=0.038). ALI in sepsis was associated with higher mortality, especially when an inspiratory pressure-limited mechanical ventilation approach was not implemented.