A 67-year male presented with relapse 14 days after treatment with vancomycin for a MRSA ventriculitis. CSF samples taken at the time of relapse grew MRSA with a MIC for vancomycin of 4 mg/L by E-test and therapy with linezolid (600 mg bd) and intraventricular vancomycin (20 mg od) was initiated. Using the macrodilution E-test, the isolate was found to have sub-populations with a MIC for vancomycin of 8 mg/L and teicoplanin of 12 mg/L and a population analysis profile almost identical to the hVISA strain MU3, indicative of a hVISA strain. Concentrations of vancomycin in the CSF over the period of therapy ranged from 25.6-192.5 mg/L after intraventricular administration and those of linezolid ranged from 3.4-6.7 mg/L after intravenous administration, exceeding the MICs for this isolate. The patient made a successful recovery, with no further episodes of ventriculitis at 1-year follow-up. We report the first case of ventriculitis due to hVISA. It was successfully treated with intrathecal vancomycin and intravenous linezolid. We also believe this to be the first documented case of clinical infection due to hVISA in South Africa.