Staphylococcus epidermidis accounts for nearly one third of all cases of bacterial keratitis in certain geographic areas. Recently, the sensitivity of this organism has changed dramatically so that nearly half of nosocomially acquired systemic S epidermidis infections are resistant to methicillin sodium, cephalosporins, and aminoglycosides. Methicillin-resistant and gentamicin sulfate-resistant S epidermidis causing infectious blepharoconjunctivitis and endophthalmitis has previously been reported. Two cases of methicillin- and gentamicin-resistant S epidermidis keratitis occurred that were treated successfully with topical vancomycin hydrochloride.