ObjectivesAs infection is a severe complication of Ommaya reservoirs (OR), and existing data is limited, herein we describe the largest study of the clinical manifestations and treatment outcomes of Ommaya reservoir-related infections (ORRI). MethodsWe retrospectively reviewed the records of all patients at our institution who had an OR placed, and developed a definite device-related infection between 2001 and 2011. ResultsAmong 501 OR placements, 40 patients (8%) developed an ORRI. These presented with meningitis and/or meningoencephalitis (60%), cellulitis (20%), or a combination thereof (20%). Approximately 40% occurred ≤30 days of OR placement, while 60% occurred ≤10 days after the device was last accessed. Only 20% presented with leukocytosis, while another 18% had a normal cerebrospinal fluid (CSF). Gram-positive skin flora accounted >80% of the pathogens. The median hospital stay and duration of antibiotics were 13 and 24 days, respectively. Although mortality rates (≈10%) were similar among all treatment groups (p > 0.99), shorter hospitalization and antimicrobial treatment durations were obtained with early versus late device removal (p < 0.038). ConclusionsAs clinical symptoms can be non-specific and CSF parameters may be within normal limits, a high suspicion for infection is required. The shortest hospitalization and treatment course was achieved with early device removal.