Mechanical ventilation after bone marrow transplantation is associated with a high mortality rate. The available literature provides conflicting predictors of outcome in relatively small study groups. To identify predictors of death and mortality trends in mechanically ventilated transplant recipients. Nested case–control study. The Fred Hutchinson Cancer Research Center in Seattle, Washington, which specializes in bone marrow transplantation. All survivors (cases, n = 53) and a group of patients matched for year of transplantation who did not survive (controls, n = 106) were selected from all mechanically ventilated patients (n = 865) who received a bone marrow transplant between January 1980 and July 1992. Patients who received mechanical ventilation for less than 24 hours after a procedure or who received mechanical ventilation after a second bone marrow transplantation were excluded. Surviving patients were defined as those who were alive 30 days after extubation and who were discharged from the hospital. Daily laboratory, physiologic, and treatment variables were collected. Survival was statistically associated with younger age, lower score on the Acute Physiology and Chronic Health Evaluation III, and a shorter time from transplantation to intubation. There were no survivors among an estimated 398 patients who had lung injury and either required more than 4 hours of vasopressor support or had sustained hepatic and renal failure. Through the use of these factors, an accurate prediction of death could have been made in the first 4 days of mechanical ventilation for more than half of the patients who did not survive. During the past 5 years, survival rate has changed from 5% to 16% (P = 0.008), an increase that was not explained by changes in the age of the patients, the rate or timing of intubation, or the percentage of allogeneic transplants that were not HLA-identical. Of the patients who required mechanical ventilation after bone marrow transplantation, no one survived with lung injury combined with either hemodynamic instability or hepatic and renal failure. However, survival after mechanical ventilation seems to be improving.