Although some data suggest favorable outcomes with use of etanercept for treatment of transplantation-related lung injury, concerns, such as development of new infections, still exist. The objective of this study was to describe the usage of etanercept at our institution and to evaluate the efficacy and safety of etanercept for this indication. Adult patients receiving at least one dose of etanercept for the treatment of pulmonary complications in patients after hematopoietic stem cell transplant from January 2005 to December 2010 were retrospectively evaluated. Outcomes included hospital mortality, incidence of new infection after etanercept administration, and time from administration of first dose of etanercept to infection. Seventeen patients who received etanercept at our institution from January 2005 to December 2010 were included. Four patients (24%) survived their hospital stay, and 3 patients (18%) were alive at both 100 days and 1 year from the initiation of etanercept therapy. Four patients (24%) developed at least one confirmed new infection after the initiation of etanercept therapy. Both moderate and long-term survival in our cohort was low. Caution and careful assessment of the risks and benefits of therapy should be taken before initiation of etanercept for transplantation-related lung injury.