To explore if the time inside the mutant selection window (T) is a reliable predictor of emergence of bacterial resistance to linezolid, mixed inocula of each of three methicillin-resistant Staphylococcus aureus strains (MIC of linezolid 2 μg ml) and their previously selected resistant mutants (MIC 8 μg ml) were exposed to linezolid pharmacokinetics using an in vitro dynamic model. In five-day treatments simulated over a wide range of the 24-h area under the concentration-time curve (AUC) to the MIC ratio, mutants resistant to 4 × MIC of antibiotic were enriched in a T-dependent manner. With each strain, T relationships with the area under the bacterial mutant concentration-time curve (AUBC) exhibited a hysteresis loop, with the upper portion corresponding to the time above the mutant prevention concentration (MPC; T) of 0 and the lower portion-to the T > 0. Using AUBC related to the maximal value observed with a given strain (normalized AUBC) at T > 0, a strain-independent sigmoid relationship was established between AUBC and T, as well as T (r 0.99 for both). AUC/MIC and AUC/MPC relationships with normalized AUBC for combined data on the three studied S. aureus strains were bell-shaped (r 0.85 and 0.80, respectively). These findings suggest that T at T > 0, T, AUC/MIC and AUC/MPC are useful bacterial strain-independent predictors of the emergence of staphylococcal resistance to linezolid.