Staphylococcus aureus is the predominant pathogen in complicated skin/skin structure infections. In this analysis of a subgroup of data from a randomised, double-blind trial, the efficacy of ertapenem 1 g daily was compared with piperacillin-tazobactam 3.375 g Q6H for treatment of complicated skin/skin structure infections caused by methicillin-susceptible S. aureus (MSSA). Of the 529 treated patients in this trial, 185 (35.0%) had MSSA as a baseline pathogen. At the test of cure assessment 10-21 days post-therapy, 54 of 67 (80.6%) protocol evaluable patients in the ertapenem group and 55 of 68 (80.9%) in the piperacillin-tazobactam group were cured (odds ratio: 1.0 (95% confidence interval (CI): 0.4-2.4), P = 0.99). In both treatment groups, cure rates were higher in patients with monomicrobial than polymicrobial infections, but the difference was not significant. In this subgroup analysis of patients with MSSA complicated skin/skin structure infections, therapy with ertapenem 1 g daily was as effective as piperacillin-tazobactam 13.5 g divided in four daily doses.