Levofloxacin (LVFX) is widely used for antibacterial prophylaxis during neutropenia. Garenoxacin (GRNX), which has been investigated in Japan, has stronger antibacterial activity than LVFX against gram-positive bacteria; however, no studies have compared the effectiveness of LVFX and GRNX. We retrospectively analyzed 42 patients with acute leukemia and 32 patients who underwent hematopoietic cell transplantation. Thirty-one patients before September 2009 received GRNX, and subsequent 43 patients received LVFX. We compared the cumulative incidences of positive blood and stool cultures. There was no significant difference in the incidence of bacteremia between the GRNX and LVFX groups. However, while gram-negative bacteria were detected in 80% of the patients with bacteremia in the GRNX group, they were detected in only 33% of the patients with bacteremia in the LVFX group. Patients in the GRNX group more frequently experienced positive stool cultures than those in the LVFX group, and this was confirmed by a multivariate analysis. Gram-negative bacteria accounted for 100 and 67% of the stool culture results in the GRNX and LVFX groups, respectively. While both fluoroquinolones may be appropriate antibacterial prophylactic agents for neutropenia patients with hematological malignancies, vigilance for gram-negative bacterial infections should be exercised when GRNX is used as prophylaxis.