The prognostic significance of a neutrophil elastase inhibitor, sivelestat sodium hydrate (SSH), was evaluated in patients on mechanical ventilation due to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) associated with systemic inflammatory response syndrome (SIRS). We studied 20 consecutive patients in our hospital, where patients complicated with interstitial pneumonia (IP) were separately analyzed (ARDS group, n = 10; IP group, n = 10). There was no significance difference between the two groups in the average lung injury score (3.0 in the ARDS group versus 2.8 in the IP group), the mean P/F ratio (96.3 mmHg in the ARDS group versus 96.7 mmHg in the IP group), plateau pressure (30.5 mmHg in the ARDS group versus 27.0 mmHg in the IP group), ventilator-free days, the duration of intensive care unit stay, and the hospitalization period. Four ARDS patients and 5 IP patients were treated with SSH within 3 days from SIRS onset. In the ARDS group, 5 patients (50%) were complicated with 4 or more organ dysfunctions and 3 patients (30%) died. IP patients all received corticosteroid, but the mortality was significantly higher among patients with IP than among those with ARDS by Kaplan-Meier survival curves. Of the clinical variables, only the diagnosis of IP was found to be independently related to mortality by a multivariate Cox proportional-hazards analysis. We conclude that IP patients have poor life expectancy if they are treated with SSH.