Fifty-five Staphylococcus epidermidis isolates, classified as contaminants or causing device-related meningitis, from external ventricular drain (EVD) and non-EVD cerebrospinal fluid specimens were characterized. Thirty-three of 42 (78.6%) meningitis isolates were PCR-positive for ica and aap, known determinants of polysaccharide- and protein-mediated biofilm production, whereas five of 13 (38.5%) contaminants were ica- and aap-negative; 71.4% of meningitis isolates and 84.6% of contaminants produced biofilm. ica+aap+ meningitis isolates produced more biofilm than ica+aap- isolates (p 0.0020). ica+aap- isolates did not produce more biofilm than ica-aap+ isolates (p 0.4368). Apparently, ica and aap are associated with biofilm production in S. epidermidis device-related meningitis isolates.