Three patients with Staphylococcus epidermis meningitis associated with cerebrospinal fluid (CSF) shunt devices were treated with a combination of intravenous vancomycin and oral rifampin. Two of the isolates were methicillin-resistant. All patients had a favorable clinical response. Time-kill curves showed that the addition of rifampin to vancomycin resulted in enhanced bactericidal activity against all isolates when compared to either antibiotic alone. This finding suggests that the combination of oral rifampin and intravenous vancomycin may be useful in the treatment of methicillin-resistant and recalcitrant methicillin-sensitive S. epidermis meningitis associated with CSF shunts. In vitro susceptibility testing should be performed.