Background Preclinical studies suggest that exogenous surfactant may be of value in the treatment of the acute respiratory distress syndrome (ARDS), and two phase 2 clinical trials have shown a trend toward benefit. We conducted two phase 3 studies of a protein-contain- ing surfactant in adults with ARDS. methods In two multicenter, randomized, double-blind trials involving 448 patients with ARDS from various causes, we compared standard therapy alone with standard therapy plus up to four intratracheal doses of a recombinant surfactant protein C-based surfactant given within a period of 24 hours. results The overall survival rate was 66 percent 28 days after treatment, and the median num- ber of ventilator-free days was 0 (68 percent range, 0 to 26); there was no significant difference between the groups in terms of mortality or the need for mechanical ventila- tion. Patients receiving surfactant had a significantly greater improvement in blood oxygenation during the initial 24 hours of treatment than patients receiving standard therapy, according to both univariate and multivariate analyses. conclusions The use of exogenous surfactant in a heterogeneous population of patients with ARDS did not improve survival. Patients who received surfactant had a greater improvement in gas exchange during the 24-hour treatment period than patients who received stan- dard therapy alone, suggesting the potential benefit of a longer treatment course. abstract