Quinupristin-dalfopristin, a novel streptogramin antibiotic, has proven efficacious against multi-drug-resistant, Gram-positive bacteria, particularly glycopeptide-resistant coagulase-negative staphylococci (CoNS), and CoNS within biofilms. We examined its activity, along with the glycopeptide antibiotic vancomycin, against laboratory-derived, vancomycin-resistant (van R) CoNS and their vancomycin-susceptible (van S) parent strains, both in the planktonic state and after their adhesion to silicone urinary catheters. The laboratory-derived van R CoNS displayed lower adhesion and biofilm formation capabilities than did their van S parent strains. Compared with silicone, the adhesion to hydrogel-silver urinary catheters was approximately one log lower for both van R and van S CoNS. Adhesion of van R and van S CoNS to silicone catheters increased their tolerance to vancomycin. However, adhered van R CoNS succumbed to concentrations of quinupristin-dalfopristin markedly (16- to 32-fold) lower than adhered van S CoNS. This anomaly may be due to the presence of vancomycin sequestered in the cell wall of van R CoNS. Quinupristin-dalfopristin in combination with vancomycin may provide enhanced inhibitory effects against van R CoNS in the adhered state.