Siddiqui NS, et al. - Since Clostridium difficile infection (CDI) has recently attracted attention as the most common hospital-acquired infection, researchers in Febrile Neutropenia (FN) have assessed the national burden and outcomes of CDI. For all subjects with FN discharge diagnosis with or without CDI (ICD-9 codes 288.00, 288.03,780.60, and 008.45), the National Inpatient Sample (NIS) database was analyzed as primary or secondary diagnosis between 2008 and 2014. A total of 19,422 discharges of FN patients with CDI occurred from 2008 to 2014. CDI incidence in FN patients increased from 4.11% (in 2008) to 5.83% (in 2014). In-hospital mortality showed a decreasing trend from 7.79% (in 2008) to 5.32% (in 2014), likely due to diagnostic and treatment improvements. In hospitalized FN patients with underlying hematological malignancies, despite the significant decrease in mortality, the incidence of CDI is increasing. In febrile neutropenia patients with CDI, age over 65, Hispanic race, hematological malignancies, urban hospital settings, and sepsis were significant mortality predictors. Modification of the risk factor, with the best possible empirical antibiotic regime, is imperative in this cohort to reduce the cost of mortality and health care.