Background: This study aims to evaluate the efficacy of combined intraventricular and intravenous co-administration of colistin and tigecycline in the management of pan-drug resistant Acinetobacter baumannii meningitis/ventriculitis. Methods: In this case series we report 3 patients with healthcare-associated ventriculitis/meningitis caused by pan-drug resistant Acinetobacter baumannii that were treated with combined colistin and tigecycline administration through both intraventricular and intravenous routes. Results: All patients were administered colistin intraventricularly at a dose of 250.000 IU q.d. and intravenously at 9 million IU loading dose, followed after 12 hours by maintenance dose of 4.5 million IU every 12 hours and tigecycline intraventricularly at a dose of 10 mg b.i.d. and intravenously at 200 mg loading dose followed after 12 hours by 100 mg every 12 hours. In patients with a calculated creatinine clearance of less than 60 ml/min, according to the Cockcroft-Gault formula, the maintenance dose of colistin was reduced based on a modified formula. All patients had a favourable clinical and microbiological response with evidence of CSF sterilization. Conclusions: Taking advantage of the synergistic action of combined colistin and tigecycline through administration both intraventricularly and intravenously may be a promising salvage option for critically ill patients with pan-drug resistant A. baumannii CNS infection.