Patients with hematological malignancies and aplastic anemia become complicated by critical infections, which are one of the common causes of death in many cases. This is a retrospective investigation of the factors that affect the efficacy of antibiotic treatment of febrile neutropenia (FN). The subjects consisted of 98 cases that developed FN during their hospitalization in this department and received antibiotics as a first-line treatment. Parameters evaluated were age, gender, with or without administration of granulocyte-colony stimulating factor (G-CSF), with or without hematopoietic transplantation, the number of antibiotics, the type of antibiotics, the highest level of C-reactive protein (CRP), with or without antifungal prophylaxis, the duration of neutropenia, and the number of neutrophils before and after the administration of antibiotics. Logistic analysis was used for statistical evaluation. With univariate analysis, significant clinical efficacy was observed with the use of carbapenems (p = 0.0009, Odds; 4.58) when the number of neutrophils was not less than 500/microL (P < 0.0001, Odds: 14.1) after administration of antibiotics. Furthermore, even when multivariate analysis was performed, significant clinical efficacy was observed independently in the use of carbapenems (P = 0.02, Odds: 3.73) and when the number of neutrophils was not less than 500/microL (P < 0.0001, Odds: 10.4) after administration of antibiotics. In this investigation, as a first-line treatment of FN, carbapenem antibiotic is recommended as a primary choice, when the number of neutrophils was expected to decrease after administration.