Background: The aim of this study was to evaluate the occurrence of febrile neutropenia (FN) during aplasia after haematopoietic stem cell transplantation (HSCT) in patients who received anti-bacterial prophylaxis with norfloxacin/ceftriaxone or ciprofloxacin, between September 2006 and May 2009. Methods: We retrospectively examined all patients undergoing HSCT at S?o Paulo Hospital during the study period. Results: Of the 107 studied patients, 71 (66.3%) were included in the analysis. The exclusion criteria were as follows: occurrence of fever or infection before the transplantation (17), prophylactic use of norfloxacin (6), fever of probable non-infectious aetiology (2), and absence of prophylaxis during the aplasia period (11). Thirty-eight patients received norfloxacin and ceftriaxone as prophylaxis (Group I) and 33 received ciprofloxacin (Group II). The groups were comparable with respect to age, underlying diseases, comorbidities, and status of the underlying disease. Patients in Group II used antibiotics in a significantly higher frequency than those in Group I (66.7% vs 33.8%, p = 0.017), for 30 days before transplantation. The number of previous hospitalisations, length of hospitalisation until transplantation, type of transplant, progenitor cells used, number of CD34 cells infused, type of conditioning, and graft-versus-host disease prophylaxis were similar in both groups. After the transplantation, 28.9% and 39.4% of the patients in Groups I and II, respectively, presented Grade III and IV mucositis (p = 0.448). Neutropenia of <500 neutrophils/mm3 lasted an average of 9.5 and 9.3 days in Groups I and II, whereas neutropenia of <100 neutrophils/mm3 lasted between 6.6 and 5.7 days. FN occurred in 78.9% of patients in Group I and 81.8% in Group II, with no significant difference in the classification of these episodes. Six patients (15.8%) in Group I and five (15.2%) in Group II had bacteraemia. All patients who did not receive prophylaxis developed FN. Conclusions: The high incidence and classification of FN episodes were similar between groups; however, the frequency was lower than in those patients who did not receive prophylaxis.