Brain abscesses are associated with high morbidity and mortality rates. In particular, patients with intraventricular rupture of brain abscess (IVROBA) exhibit mortality rates up to 85%. Treatment options are lacking for IVROBA, once patients become refractory to intravenous antibiotics and surgical drainage. Limited data exist regarding the risks and benefits of intraventricular therapy in such a scenario. We report a patient with IVROBA, who deteriorated while on systemic antibiotics; once intraventricular vancomycin was employed, the patient demonstrated remarkable improvement without perceivable side effects. This case suggests that intraventricular vancomycin may be a safe, effective, and viable option for the treatment of IVROBA, especially for patients becoming refractory to systemic antibiotics.