Development of new broad-spectrum antibiotics that are effective against both gram-positive and gram-negative bacteria could improve treatment choices for bacterial skin and skin structure infections (ABSSSIs). Ceftobiprole is an advanced-generation intravenous cephalosporin that has extensive in vitro efficacy against both gram-positive and gram-negative bacteria (including methicillin-resistant Staphylococcus aureus). The TARGET study compared ceftobiprole to vancomycin + aztreonam in a randomized, double-blind, active-controlled, parallel-group, multicenter, phase 3 noninferiority trial. Early clinical response 48–72 hours after treatment initiation in the intent-to-treat (ITT) population was the primary efficacy endpoint defined by the Food and Drug Administration. In contrast, the European Medicines Agency defined investigator-assessed clinical success at the test-of-cure (TOC) visit. The lower limit of the 95% CI for the difference in success rates (ceftobiprole versus vancomycin/aztreonam more than −10%) was considered noninferiority. Adverse event reporting and laboratory data collection were used to assess safety. Ceftobiprole (n=335) or vancomycin/aztreonam (n=344) were given to a total of 679 patients. Early clinical success rates in the ceftobiprole and vancomycin/aztreonam groups were 91.3% and 88.1%, respectively, with noninferiority (adjusted difference: 3.3%; 95% CI: 1.2, 7.8). Noninferiority was demonstrated for both the ITT (90.1% vs. 89.0%) and clinically evaluable (97.9% vs. 95.2%) populations, and investigator-assessed clinical success at the TOC visit was similar across the 2 groups. Microbiological success and safety profiles were similar in both treatment groups. In terms of early clinical response and investigator-assessed clinical outcome at the TOC visit, TARGET showed that ceftobiprole is non-inferior to vancomycin/aztreonam in the treatment of ABSSSIs.