Abstract: Correctly determined susceptibility breakpoints are important to both the individual patient and to society at large. A previously derived patient population pharmacokinetic model and Monte Carlo simulation (9999 patients) were used to create a likelihood distribution of tigecycline exposure, as measured by the area under the concentration–time curve at 24 h (AUC24). Each resultant AUC24 value was paired with a clinically relevant fixed MIC value ranging from 0.12 to 2 mg/L. For each AUC24–MIC pair, the probability of microbiologic response was calculated using an exposure–response relationship, which was derived from patients with complicated skin and skin structure infections that involved Staphylococcus aureus or streptococci or both. The median probability of microbiologic success was 94% or greater for MIC values up to and including 0.25 mg/L. The median probability of microbiologic success was 66% or less for MIC values of 0.5 mg/L or greater. These data support a susceptibility breakpoint of 0.25 mg/L for S. aureus and streptococci. [Copyright &y& Elsevier]