BACKGROUNDHospitalization for febrile neutropenia (FN) in cancer patients is associated with considerable morbidity, mortality, and cost. The study was undertaken to better define mortality, length of stay (LOS), cost, and risk factors associated with mortality and prolonged hospitalization in cancer patients with FN.METHODSThe longitudinal discharge database derived from 115 US medical centers was used to study all adult cancer patients hospitalized with FN between 1995 and 2000, comprising a total of 41,779 patients. Primary outcomes included mortality, LOS, and cost per episode.RESULTSOverall, in‐hospital mortality was 9.5%. Patients without any major comorbidities had a 2.6% risk of mortality, whereas 1 major comorbidity was associated with a 10.3% and more than 1 major comorbidity with a ≥21.4% risk of mortality, respectively. Mean (median) length of stay was 11.5 (6) days, and the mean (median) cost was $19,110 ($8,376) per episode of FN. Patients hospitalized for ≥10 days (35% of all patients) accounted for 78% of overall cost. Independent major risk factors for inpatient mortality included invasive fungal infections, Gram‐negative sepsis, pneumonia and other lung disease, cerebrovascular, renal, and liver disease. Main predictors for LOS ≥10 days included leukemia, invasive fungal infections, other types of infection, and several comorbid conditions.CONCLUSIONFactors associated with increased mortality, LOS, and cost in hospitalized adult cancer patients with FN include patient characteristics, type of malignancy, comorbidities, and infectious complications. These factors may be useful in identifying patients at increased risk of serious medical complications and mortality for more aggressive supportive care measures. Cancer 2006. © 2006 American Cancer Society.