Respiratory failure was measured as the institution of assisted mechanical ventilation for hypoxemic (oxygenation) or hypercarbic (ventilatory) failure after marrow transplantation. There were 348 (23%) marrow recipients who required mechanical ventilation for an average of 8 days (median, 5; range, 1 to 45). The average onset of mechanical ventilation was 39 days (median, 22; range, 0 to 172) after transplantation. Factors previously found to be associated with mechanical ventilation were tested in a Cox proportional hazards model. Older age, active malignancy at time of transplantation, and donor-recipient marrow HLA-non-identity were independent risks for assisted mechanical ventilation after marrow transplantation. Twenty-one percent (n = 72) of the marrow recipients receiving assisted mechanical ventilation for respiratory failure were extubated. Four percent (n = 15) were discharged from the hospital, and 3% (n = 10) survived 6 months after transplantation. All of these survivors were physically functional. Three had mild chronic respiratory symptoms and restrictive or obstructive airflow defects 1 yr after transplantation. Respiratory failure requiring assisted mechanical ventilatory support occurs in 23% of marrow recipients and is associated with functional survival at 6 months in 3%. Older age, active malignancy at time of transplantation, and donor-recipient marrow HLA-non-identity are risk factors for subsequent respiratory failure. In view of the poor prognosis associated with respiratory failure, these factors should be considered when counseling patients and families regarding this mode of treatment.