To date, no study has been specifically designed to identify determinants of death in neutropenic cancer patients presenting with acute respiratory distress syndrome (ARDS). The aim of this study was to identify early predictive factors of 28-day mortality in these patients. Factors associated with 28-day mortality during intensive care unit (ICU) stay were also described. 70 consecutive cancer patients with ARDS and neutropenia were prospectively analysed over a 6-yr period. Mortality at 28 days was 63%. Factors independently associated with good prognosis were: lobar ARDS (OR 0.10, 95% CI 0.02-0.48), use of initial antibiotic treatment active on difficult to treat bacteria (ticarcillin-resistant Pseudomonas aeruginosa, Stenotrophomonas maltophilia or extended-spectrum β-lactamase-producing strains) (OR 0.08, 95% CI 0.02-0.33) and first-line chemotherapy (OR 0.08, 95% CI 0.02-0.37). During the ICU stay, mortality was associated with the markers of organ dysfunctions, the absence of neutropenia recovery and the use of vasopressors. During the first 3 weeks, the conditional probability of discharge alive from ICU did not decrease. At ICU admission, first-line chemotherapy, lobar ARDS and antibiotic treatment active on difficult-to-treat bacteria were associated with survival. During ICU stay, mortality was associated with organ dysfunctions and use of vasopressors. Most survivors have an ICU stay of >3 weeks.