In febrile neutropenia, either linezolid (LIN) or vancomycin (VAN) can be used if a gram-positive infection is suspected. Interestingly there is no literature in which both are compared in the setting of febrile neutropenia. Therefore, we provide here the results of a retrospective analysis of adding VAN versus LIN in patients with febrile neutropenia. Patients with haematological diseases and febrile neutropenia after myelosuppressive chemotherapy and no clearance of infection after the first empiric broad-spectrum antibiotic were escalated to VAN or LIN from 03/2010 to 03/2014 at the University Hospital Bonn were included in this retrospective analysis. Out of the 73 patients, 50 had received VAN and 23 LIN. The median hospitalisation time in the LIN cohort was significantly shorter than in the VAN cohort (LIN 16 days vs VAN 20 days p=0.046). Successful defervescence with the escalation to VAN or LIN could be detected in 76% of the LIN cases and 50% in the VAN group (p=0.052). This trend to better efficacy with LIN was also shown by a higher rate of discontinuation of VAN and escalation to another antibiotic scheme (54.2%) than in the LIN cohort (24%, p=0.052). The antibiotic therapy in febrile neutropenia with LIN showed a trend of better efficacy than therapy with VAN. However, because of the small sample size and the retrospective manner, VAN may still be considered a reasonable option in neutropenic fever, and randomised studies are needed in this field.