Staphylococcus epidermidis has emerged as a major nosocomial pathogen that is often associated with infections of indwelling medical devices. Microbial adhesion to implanted foreign materials is a prerequisite for establishing infection. We studied the time-dependent anti-adhesion effects of linezolid and vancomycin on three S. epidermidis clinical isolates. Minimum inhibitory concentration (MIC) values were identical for both agents for all three isolates (2 mg/l). Bacterial suspensions were added to polystyrene wells and treated with 0.5-4 times the MIC of linezolid or vancomycin at 0, 2, 4 or 6 h post-inoculation. Supra-inhibitory (2 and 4 x MIC) and inhibitory (MIC) concentrations of linezolid demonstrated potent anti-adhesion activity following 2 and 4 h deferred treatments. Even at sub-inhibitory concentrations (0.5 x MIC), suppression of staphylococcal adherence to polystyrene was still evident in most cultures. Linezolid at two and four times the MIC also exerted significant inhibitory effects in cultures that had been treated with a 6-h delay. Supra-inhibitory and inhibitory concentrations of vancomycin administered 2 h post-infection appeared equally effective as linezolid. However, sub-inhibitory concentrations of vancomycin showed minimal or no activity against bacterial adhesion. When vancomycin treatments were delayed by 4 h, only concentrations above the MIC prevented adherence. Linezolid has promising in vitro anti-adhesion activity that merits further studies to determine its role in the management of foreign-body infections.