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Background: Evidence for the effectiveness of linezolid in neurosurgical infections (NSIs) is growing. The comfortable oral dosage and tolerance of linezolid opens the possibility for sequential antimicrobial treatment (SAT) in stable patients after a period of intravenous treatment., Methods: To evaluate the efficacy and safety of SAT with oral linezolid in patients with NSI and to analyse the cost implications, an observational, non-comparative, prospective cohort study was conducted on clinically stable consecutive adult patients at the Neurosurgical Service. Following intravenous treatment, patients were discharged with SAT with oral linezolid., Results: A total of 77 patients were included. The most common NSIs were: 41 surgical wound infections, 20 subdural empyemas, 18 epidural abscesses, and 16 brain abscesses. Forty-four percent of patients presented two or more concomitant NSIs. Aetiological agents commonly isolated were: Propionibacterium acnes (36 %), Staphylococcus aureus (23 %), Staphylococcus epidermidis (21 %) and Streptococcus spp. (13 %). The median duration of the SAT was 15 days (range, 3-42). The SAT was interrupted in five cases due to adverse events. The remainder of the patients were cured at the end of the SAT. A total of 1,163 days of hospitalisation were saved. An overall cost reduction of €516,188 was attributed to the SAT. Eight patients with device infections did not require removal of the device, with an additional cost reduction of €190,595. The mean cost saving per patient was €9,179., Conclusions: SAT with linezolid was safe and effective for the treatment of NSI. SAT reduces hospitalisation times, which means significant savings of health and economic resources.