We developed a clinical decision support system--ventilation protocols--that managed tidal volume and ventilator rate settings during mechanical ventilation of patients with the Adult Respiratory Distress Syndrome (ARDS). We applied these protocols for a total of 10,903 hours in 40 ARDS patients. The clinical staff suspended the protocols for only 5% of the total application time due to medical procedures, surgeries, transient clinical problems not addressed by the protocols, or because of attending physician request. Of 3,148 instructions generated by the ventilation protocols, the clinical staff followed 2,932 (93%). The staff did not follow some instructions because of patient data errors, computer software and protocol logic errors, inability of the clinical staff to implement protocol instructions because of more pressing duties, and clinical staff objections to specific instructions. Sixty percent of the patients treated by the ventilation protocols survived. Our results demonstrate that the ventilation protocols provided a practical and safe decision support system for the mechanical ventilation of ARDS patients.