MICs and minimum bactericidal concentrations (MBCs) of daptomycin, vancomycin, linezolid and quinupristin–dalfopristin (Q-D) were determined for 108 staphylococcal isolates. All strains were susceptible (MICs) to daptomycin (2.0 mg/L) and Q-D (1.0 mg/L). All but three isolates were susceptible to vancomycin (4.0 mg/L) and all but one methicillin-resistant Staphylococcus aureus strain were susceptible to linezolid (4.0 mg/L). Q-D had the lowest geometric mean MIC (0.29 mg/L) and daptomycin had the lowest geometric mean MBC (0.57 mg/L). Time–kill tests were performed on 25 isolates. Bactericidal activity (>99.9% kill) was observed with daptomycin at 2 mg/L and at 2 × MBC for 92% of strains tested. In comparison, the bactericidal rates for the other drugs at breakpoint concentrations and at 2 × MBC were 72% and 70% for vancomycin, 46% and 60% for Q-D, and 7% and 14% for linezolid. Of the four drugs tested, daptomycin was bactericidal against the most strains and had the most rapid cidal activity.