The aim of this work is to evaluate the outcome of patients treated with intrathecal colistin for meningitis/ventriculitis. This retrospective case series study included patients presenting with nosocomial meningitis/ventriculitis following neurosurgical interventions and having intravenous (IVC group) or intravenous and intrathecal/intraventricular colistin (ITC group) treatment between 2006 and 2014. Thirty-four patients presented nosocomial meningitis/ventriculitis; 11 (32.5 %) were included in the IVC group and 23 (67.6 %) in the ITC group. The most frequent isolated bacteria were Acinetobacter baumannii. The mean dose was 170,000 (±400) IU and the duration of intraventricular treatment was 16.0 (±8.3) days. The duration of intravenous treatment was 16.0 (±8.3) days in the ITC group and 15.3 ± 7.6 days in IVC group. Hospital mortality was significantly lower in the ITC group compared with the IVC group (13 vs. 72.7 %, p = 0.001). The combination of intravenous plus intraventricular (IV-IVT) colistin therapy may improve outcomes in patients attending with meningitis/ventriculitis due to multi-drug resistance infections.